Omeprazole as a diagnostic tool in gastroesophageal reflux disease

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.     

Gastric emptying as an etiopathogenic factor in gastroesophageal reflux disease

The aim of this study is to evaluate gastric emptying change in patients with gastroesophageal reflux (GER). To this purpose, 36 patients with GER diagnosis and 18 control subjects have been studied. GER diagnosis was achieved by means of endoscopy, biopsy and 24 h continuous pH monitoring. Gastric emptying studies were performed on a two day basis, similar labelling meals were provided to patients and control subjects. Those consisted in a one-egg omelette, chicken (110 gr) and orange juice (200 ml). On first day liquid phase was labelled with 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), and on second day, the solid phase was labelled with 99mTc-sulfur colloid in the omelette (Labelling efficiency was 85.3 +/- 3.2%). The studies were carried out by imaging static anterior and posterior views every 20 minutes for a total of 180 minutes. Images were quantified obtaining solid and liquid gastric emptying curves. No statistical significative difference between patients and control subjects gastric emptying results were found. We can conclude that gastric emptying is not a main factor in the pathogenesis of gastroesophageal reflux.     

A prospective assessment of gastroesophageal reflux before and after treatment of achalasia patients: pneumatic dilation versus transthoracic limited myotomy

OBJECTIVES: We conducted this study to determine whether reflux should be a major consideration in the choice of treatment for achalasia patients. Achalasia patients undergoing either pneumatic dilation or transthoracic limited esophagomyotomy were monitored for reflux before and after treatment, for comparison. METHODS: Twenty-four hour ambulatory esophageal pH tests and esophageal manometry were performed on 32 consecutive, untreated achalasia patients. Studied (before and after treatment) were 17 patients who underwent pneumatic dilation and 15 patients who received transthoracic limited myotomy without fundoplication. All follow-up studies were completed within 12 months of treatment. RESULTS: The ages of the two groups were not significantly different (p > 0.05, 45 +/- 9 yr myotomy vs. 44 +/- 13 yr dilation). The resting lower esophageal sphincter pressure was not significantly different (p > 0.05 before treatment) between groups but was reduced significantly (p < 0.05 after treatment) in both groups (30 +/- 9 mm Hg before vs. 9 +/- 4 mm Hg after myotomy, and 27 +/- 10 mm Hg before vs. 11 +/- 4 mm Hg after pneumatic dilation. The total time the pH was < 4.0 was not significantly different, p > 0.05, in either group before treatment (myotomy, 3.7 +/- 4.4%; dilation, 2.9 +/- 4.9%) or after treatment (myotomy, 8.6 +/- 9.2%; dilation, 10.2 +/- 15.9%). Twelve of 32 patients (38%), had a percent total time < 4.0 that exceeded 6% after treatment, eight of whom were asymptomatic. CONCLUSIONS: These results indicate that the amount of reflux after treatment by both pneumatic dilation and transthoracic esophagomyotomy is similar. The absence of reflux symptoms in treated achalasia patients does not exclude the possibility of significant acid reflux.     

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, in fact, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.     

Surgical treatment of gastroesophageal reflux disease

Antireflux surgery is successful in 85-90% of eligible patients, with relief of symptoms, cure of oesophagitis and possibly prevention of progression of the dysplasia in a Barrett's oesophagus. The mortality in the latest publications is given as 0.05%. The morbidity, apart from recurrences, is not yet sufficiently known. Some 250 antireflux operations are performed annually in the Netherlands, fewer than 20% of the estimated requirement of 10 operations per 100,000 of the population per year, and also fewer than in Scandinavia. Nissen fundoplication (folding the fundus of the stomach around the entire circumference (360 degrees) of the oesophagus) is generally accepted as the standard primary operation. Nissen fundoplication during laparoscopy seems to be just as good. Results of randomized clinical trials will have to be awaited to prove this assumption. Belsey's operation (folding the fundus around 270 degrees of the circumference of the oesophagus via thoracotomy) is nowadays performed almost exclusively in recurrent reflux disease and in persistent dysphagia after a primary operation.     

Surgical treatment of gastroesophageal reflux disease

Modern techniques have substantially improved the outcome of surgical therapy for reflux. Surgery, therefore, should not be considered a method of last resort but instead a reasonable alternative to treat patients with abnormal reflux. Adequate preoperative staging of the disease helps design the most appropriate operation. Minimally invasive techniques improve exposure and enhance recovery. Control of symptoms is achieved in the great majority of patients, and complications are minimal if the operation is performed following basic principles of sound operative technique.     

Anorexia as the main symptom of gastroesophageal reflux: case study of a 13.5-year-old girl

13.5-year-old girl who was admitted to hospital because of anorexia nervosa started to complain of abdominal pain in her 3-rd week of hospitalization. She underwent 24-hour pH-metry and upper GI endoscopy. These procedures showed that GER was the cause of anorexia. Therapeutic management led to marked improvement.     

Respiratory manifestations of gastroesophageal reflux in children

Gastroesophageal reflux is often overlooked as both a cause and a complication of respiratory disease in children. The manifestations may be protean and may bear little clinical relationship to the gastrointestinal tract. However, a high index of suspicion for its potential role in unexplained respiratory symptoms may yield large benefits for the physician and patient alike.     

Severity of esophageal eosinophilia predicts response to conventional gastroesophageal reflux therapy

The purpose of this study was to examine the safety and efficacy of fluvoxamine in the treatment of psychogenic (neurotic) skin excoriation. Fourteen subjects with psychogenic excoriation were given fluvoxamine in a 12-week, open-label trial after completion of the Structured Clinical Interview for DSM-IV. All subjects met DSM-IV criteria for at least one comorbid psychiatric disorder, with mood disorder the most common. Most subjects' excoriation had features of an impulse control disorder. Both completers (N = 7) and the entire group had significant improvement on the modified Yale-Brown Obsessive Compulsive Scale but no improvement on the Hamilton Rating Scale for Depression. In the self-report data, the seven completers had significant reduction in behaviors involving the skin (e.g., scratching, picking, gouging, or squeezing) and in global assessment of symptoms. Endpoint analysis of all 14 subjects' self-report data demonstrated significant improvement in the presence of skin sensations, skin appearance and lesions, behaviors involving the skin, control over skin behavior, and global assessment. The results of this preliminary open trial suggest that fluvoxamine may be effective in reducing psychogenic excoriation, and this effect seems to be independent of mood. Controlled studies are needed to confirm these findings.     

Evaluation of laparoscopic Toupet fundoplication as a primary repair for all patients with medically resistant gastroesophageal reflux

BACKGROUND: This prospective study assesses the outcome results in 100 consecutive patients with gastroesophageal reflux disease (GERD) treated with a laparoscopic Toupet fundoplication. METHODS: GERD was confirmed by 24-h pH study and/or esophagogastroduodenoscopy (EGD). Pre- and postoperative symptoms, operative times, and perioperative complications were recorded on standardized data forms. Early follow-up was at 3 months and late follow-up, including 24-h pH, manometry, and EGD was at 22 months. RESULTS: Preoperative symptoms included heartburn (92%), regurgitation (58%), water brash (39%), and dysphagia (39%). Mean operative time was 3.2 hours. There were no conversions to celiotomy and there were no mortalities. The perioperative complication rate was 14%; 6% (5/83) of patients reported heartburn at 3 months and 20% (15/74) at 22 months. Early and late dysphagia was 20% (17/83) and 9% (7/74), respectively; 24-h pH testing was abnormal in 90% of symptomatic patients (9/10), 39% of asymptomatic patients (12/31), and 51% overall. CONCLUSIONS: Despite early improvement in reflux symptoms following laparoscopic Toupet fundoplications, there is a high incidence of recurrent GERD. Symptomatic follow-up underestimates the true incidence of 24-h pH-documented reflux. Based on these results we cannot recommend the laparoscopic Toupet repair for GERD patients with normal esophageal motility.     

Mechanisms of gastroesophageal reflux in healthy premature infants

A seroprevalence study for poliomyelitis was carried out on a sample of sera from a serum bank used for a vitamin A study. Vaccination coverage was satisfactory (80% or more) in five of nine provinces, although a prevalence of antibody to polio of 80% or more was found in all provinces. Serologic immunity (i.e., the prevalence of neutralizing antibodies) exceeded vaccination coverage, suggesting secondary spread of vaccine virus. However, whether or not water was supplied through a piped system was not associated with secondary spread of vaccine virus to nonvaccinated children. Seroprevalence studies are a valuable adjunct to acute flaccid paralysis surveillance, which is the standard surveillance instrument for the poliomyelitis eradication initiative. The use of available and suitable serum banks for seroprevalence investigations is a relatively cheap monitoring option that can yield very valuable information for the eradication initiative.     

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease

A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin ITRA and OH-ITRA, respectively, were 287 +/- 109 ng/ml and 629 +/- 227 ng/ml at day -1 and 378 +/- 147 ng/ml and 725 +/- 242 ng/ml at day +1. The maximum Cmin values were observed at day +3. Six patients at day -1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.     

The diagnosis and management of gastroesophageal reflux disease

GERD is a common clinical problem. Generally, its clinical presentation and management are straightforward. Greater awareness of the numerous extraesophageal manifestations of the disease aids patients and physicians in appropriate recognition and treatment. Medical therapy is effective in the majority of cases but often requires long-term medication for acceptable symptom control. A small, but significant proportion of patients presents with or develops complications of GERD, most importantly Barrett's esophagus. Although the logistics of long-term surveillance of persons with Barrett's esophagus is unclear, the association of this metaplastic change with esophageal adenocarcinoma underscores the importance of regular follow-up.     

Function of the esophagus and stomach in gastroesophageal reflux

The recognition of abnormal DNA structure by proteins is fundamentally different from sequence-specific DNA binding. Recent crystal structures of uracil-DNA glycosylases show a novel uracil-binding pocket that explains the enzyme's selectivity for uracil-containing DNA and provide a structural basis for exploring the catalytic mechanism of amino-glycosylic bond cleavage.     

Modern diagnosis of gastroesophageal reflux disease (GERD)

Typical dominant symptoms such as heartburn and regurgitation are very specific for the diagnosis of GERD. Unfortunately they are relatively insensitive. The diagnosis can be made reliably if mucosal breaks are present at endoscopy. In endoscopy-negative patients with atypical symtoms, the most accurate investigation is 24-hour pH-monitoring with symptom analysis. Another alternative which may prove more cost-effective is to start with a PPI-test (e.g. omeprazole 20 or 40 mg bid for one or two weeks) and to use the symptomatic response as a diagnostic test.     

Evaluation of gastroesophageal reflux in patients with laryngotracheal stenosis

To report the incidence of pharyngeal acid reflux events in patients with laryngotracheal stenosis (LTS), we studied 12 patients with LTS and 34 healthy volunteers. All patients and controls underwent ambulatory 24-hour 3-site pH monitoring. In ambulatory pH monitoring, pH was recorded at manometrically determined sites of the pharynx, proximal esophagus, and distal esophagus. For all 3 sites, a pH value below 4 that was not related to the time of oral intake or belching was considered an acid reflux event. Eight of the 12 LTS patients exhibited pharyngeal acid reflux events. In the control group, pharyngeal acid reflux events were documented in 7 subjects. In between-group comparison, the number of reflux episodes and the percent acid exposure time in the pharynx were greater in LTS patients than in controls. Reflux parameters of the proximal and distal esophagus in LTS patients were similar to those of controls. The incidence of pharyngeal acid reflux events in LTS patients was higher than that in controls. It is suggested that identification and treatment of gastroesophageal reflux in patients will significantly simplify and improve the results of treatment for LTS.     

Effect of pneumatic dilation on gastroesophageal reflux in achalasia

The aims of this study were to assess the effect of pneumatic dilation on gastroesophageal reflux in achalasia, differentiate esophageal acid due to lactate from acid due to gastroesophageal reflux, and determine if chest pain and heartburn are reliable indicators of gastroesophageal reflux. Eight untreated achalasia patients underwent pre- and postdilation esophageal fluid/food residue lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom assessment. All patients had a successful clinical outcome and a decrease in lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients before and two patients after dilation. Postdilation acid exposure was mild. Lactate was detected before dilation in all patients. A lactate concentration >2 mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile. There was no correlation between an abnormal 24-hr pH test and age, lower esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare in untreated achalasia and esophageal acidity may result from ingestion of acidic foods or production of lactate. Mild gastroesophageal reflux occurs after dilation but is of no clinical significance. Chest pain and heartburn are not indicators of acid reflux in achalasia.