Recent topics in the medical treatment of reflux esophagitis

Reflux esophagitis is one of the most common disorders of the upper gastrointestinal tract. It can lead to obstruction through stricture formation, in more severe form to bleeding through ulceration, and to cancer development through the association of Barrett's esophagus. The vast majority of esophagitis can be managed medically. Medical management is separated into two categories: (1) life style modification and (2) drug therapy. Drug therapy includes antacids, prokinetics, sucralfate, H2 receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs). Among these, antisecretory therapy is the mainstay for the treatment. PPIs are shown to be superior to H2-RAs in healing of esophagitis and symptom relief. Recurrence, particularly of erosive esophagitis, is common without maintenance therapy. PPIs are also consistently superior to H2-RAs in maintenance of esophagitis healing. Interestingly, a recent report has suggested that curing Helicobacter pylori infection may provoke reflux esophagitis, raising the possibility that the gastroesophageal reflux diseases become more common in the future. Therefore, treatment strategy for reflux esophagitis needs to be re-established in terms of the future cost-effectiveness evaluation and quality-of-life assessments.     

Role of Helicobacter pylori in reflux esophagitis

It is now widely accepted that peptic ulcer disease (PUD) is a result of chronic infection of Helicobacter pylori (H. pylori). Thus, treatment of PUD should be aimed toward eradication of H. pylori with antibiotics. One the other hand, recent study from England suggested that eradication of H. pylori may provoke development of reflux esophagitis in duodenal ulcer patients. Despite duodenall ulcer patients with concomitant esophagitis is a specific type of esophagitis, it is important to recognize the development of reflux esophagitis after cure of H. pylori infection. Whether the development of reflux esophagitis is occurred in other H. pylori-related disease such as gastric ulcer remains to be studied.     

Evaluation by a randomized trial of the usefulness of endoscopy after treatment of a flare-up of non-severe esophagitis

OBJECTIVES: The clinical usefulness of esophageal endoscopy at the end of a treatment of non-severe esophagitis due to gastro-esophageal reflux is unknown. The aim of this randomized trial was to compare two strategies for the management of non-severe esophagitis, one with endoscopy at the end of the initial treatment including a retreatment of persistent ulcerations (group 1) and one without final endoscopy (group 2). PATIENTS AND METHODS: Eligible patients had heartburn and endoscopically proved esophagitis, non-confluent or confluent erosions and must have been relieved of their heartburn after a 4 to 6 week treatment with H2 blockers or by proton pump inhibitor. When the ulcerations were healed in group 1 and immediately at the end of the initial treatment in group 2, a self-care treatment by sodium alginate was prescribed. A total of 369 patients were randomized, 178 in group 1, 191 in group 2. RESULTS: At 6 months, there was no difference in the percentage of patients with clinical and endoscopical success, 52% and 55% in group 1 versus 47% and 60% in group 2 respectively. In group 1, 29 patients (16%) needed another treatment than alginate versus 31 patients in group 2 (16%, NS). Among patients with endoscopy at 6 months, the percentage of patients with confluent erosions was 4% (5/140) and with non-confluent erosion 26% (37/140) in group 1 versus 6% (9/158) and 22% (34/158) in group 2 respectively (NS). The percentage of patients with at least one sick day related to reflux was 12% in group 1 versus 5% in group 2 (P = 0.03). There was no difference in pharmacy costs (331,40 vs 264,3 Francs). CONCLUSION: Endoscopic verification is not necessary in patients with non-severe esophagitis who have been clinically improved by an initial treatment by H2 blockers or proton pump inhibitor, even among patients with confluent esophageal erosions.     

Gastroesophageal reflux in children: clinical manifestations, diagnosis, pathophysiology, and therapy

Gastroesophageal reflux in infants and children is a challenging diagnostic problem. A careful history and physical examination are of foremost importance. In infants, the esophageal manometry study and the Tuttle test are helpful in confirming gastroesophageal reflux. In older children, these two studies as well as the Bernstein test should be done to document reflux. The presence of esophagitis or esophageal strictures is best determined by esophagoscopy with concomitant grasp or suction biopsies. A medical regimen should be tried for three to six weeks in all children except those with esophageal strictures or severe malnutrition. Medical failures should be treated surgically with Nissen fundoplications, performed by a competent pediatric surgeon. The prognosis for children undergoing surgical correction is excellent.     

Reflux esophagitis: manometry and Ph measurement

Manometry and pH-metry are essential in the examination of functional disturbances of the esophagus. Proven indications for manometry are dysphagia of unknown origin and noncardiac chest pain; in reflux esophagitis manometry is used for measuring pressure of the lower esophageal sphincter and detecting motility disorders of the esophageal body, pH-metry is used as long-term pH-metry to quantify gastroesophageal reflux during day and night; furthermore long-term pH-metry is important in the classification of atypical esophagitis. Recording gastroesophageal reflux and esophageal motility may influence planning of therapy and predict prognosis. Before antireflux surgery manometry and pH-metry are useful in judging the clearance mechanisms of the esophagus. Used critically, manometry and pH-metry can be very helpful as cost-effective diagnostic tools in the long-term therapy of reflux esophagitis.     

Gastroesophageal fundoplication for reflux in infants and children

Fifteen infants and young children with symptomatic gastroesophageal reflux underwent fundoplication during a 6 1/2-yr period. Standard barium esophagrams clearly demonstrated reflux in only 10 of the 15 patients; however, cine esophagrams indicated reflux in the remaining patients. Esophagoscopy with mucosal biopsy demonstrated esophagitis in 9 of the 10 patients in whom it was performed, and it is a very helpful diagnostic procedure. Esophageal manometry showed low sphincter pressures in each of 7 patients. Fundoplication was performed when there was (1) persistent reflux after a 3-wk hospital course of vigorous medical management, (2) failure to gain weight, (3) malnutrition, (4) recurrent aspiration, (5) esophagitis, or (6) stricture. Concomitant gastrostomy prevented the gas bloat syndrome in all patients. All strictures were successfully relieved by postoperative dilatation (average four per patient). Esophageal replacement is rarely indicated for strictures due to reflux in children. No deaths or major complications occurred following operation. Each of the patients has been relieved of clinical reflux, and each has gained weight more rapidly than preoperatively. Follow-up esophagrams on each of the patients show absence of reflux, and manometry shows the low esophageal sphincter pressure to be increased an average of 10 mm Hg above preoperative values. Since the results of Nissen fundoplication to correct reflux in infants and young children are highly satisfactory, and since the consequences of persistent reflux may be severe, a fairly aggressive approach should be taken in the management of symptomatic reflux.     

Cloning, genomic structure, and expression of mouse ring finger protein gene Znf179

OBJECTIVE: H. pylori causes chronic gastritis, which may progress to peptic ulcer, gastric atrophy, or gastric cancer. However, little is known about the role of H. pylori infection in reflux esophagitis and the relationship between reflux esophagitis and atrophic gastritis needs to be clarified. We sought to identify the possible interrelationships among Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis, to signal areas in which researchers should consider focusing their attention. METHODS: A broad-based Medline search was performed to identify all related publications addressing H. pylori infection, atrophic gastritis, gastroesophageal reflux disease (GERD), secretion of gastric acid, and gastric motility published between 1966 and July 1997. RESULTS: Whereas some studies have shown no significant association between H. pylori infection and reflux esophagitis, others have observed that the prevalence of H. pylori infection was lower in patients with GERD, implying a protective role. Eradication of H. pylori leads to occurrence of reflux esophagitis in some cases, but the mechanisms inducing posteradication reflux esophagitis are unknown. H. pylori infection may lead to atrophic gastritis (and hence hypochlorhydia) through both bacterial and host factors, although gastric atrophy and subsequent intestinal metaplasia are hostile to H. pylori because of hypochlorhydria. Although it has been reported that long-term proton pump inhibitor therapy for refractory reflux esophagitis may induce or enhance the development of gastric atrophy in H. pylori-infected patients, this relationship has been disputed. CONCLUSIONS: H. pylori infection may be negatively associated with reflux esophagitis, but this requires confirmation. Research then needs to focus on whether this is explained through motility- or acid-related mechanisms. The potential costs of maintenance antireflux therapy may need to be taken into account when evaluating the cost effectiveness of anti-H. pylori therapy.     

Use of electron scanning microscopy and technical mechanics methods for determination of prolonged usefulness of Polfix plates after clinical use]

BACKGROUND: The ability of gastroesophageal reflux disease to provoke asthma is controversial. Recent reports have suggested that reflux to the proximal esophagus may be especially likely to aggravate asthma, but the prevalence of proximal reflux in children and adolescents is poorly documented. It is also unclear how sensitive and specific the commonly used tests of reflux, barium swallow, and scintiscan are compared with pH probe studies in young patients. There is limited information on the effectiveness of the combination of H2 blockers and prokinetic agents in controlling reflux in children. OBJECTIVE: There were three objectives in this study: (1) to determine the prevalence of both proximal and distal gastroesophageal reflux in asthmatic children and adolescents; (2) to determine the sensitivity, specificity, positive and negative predictive values of barium swallow and scintiscan studies; and (3) to determine the effectiveness of standard antireflux pharmacotherapy. METHODS: A 24-hour, 2-channel pH probe study was carried out in 79 asthmatic children aged 2 to 17 years. The prevalence of abnormal proximal and distal gastroesophageal reflux was calculated from the findings. In 63 of these patients, barium swallow and Technetium99 scintiscan were carried out and the findings used to calculate the sensitivity, specificity, positive and negative predictive value of these studies relative to pH probe. In 11 subjects a follow-up, 24-hour pH probe was carried out after at least 3 weeks of therapy with an H2 blocker and prokinetic agent to determine the efficacy of therapy. RESULTS: There was abnormal proximal esophageal reflux in 64.5% of subjects and abnormal distal reflux in 73.4%. The sensitivity, specificity, positive and negative predictive values of barium swallow were 46.1%, 83.3%, 82% and 51%, respectively. Those of scintiscan were 15%, 72.7%, 50% and 32%, respectively. Of 11 subjects studied by repeat pH probe, 10 had persistent abnormal reflux. CONCLUSION: Abnormal reflux into the proximal esophagus occurs in the majority of asthmatic children with difficult-to-control disease. The barium swallow and scintiscan compare poorly with pH probe in diagnosing reflux. Treatment of reflux with recommended does of H2 blockers and prokinetic agents has a high failure rate, and follow-up studies are essential.     

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms

OBJECTIVE: The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms. METHODS: A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy. RESULTS: There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis. CONCLUSIONS: Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barrett's esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.     

Diagnosis and management of gastroesophageal reflux in infants and children

Use of histamine blockers, proton pump inhibitors, and prokinetic drugs, along with traditional antacids, has become standard therapy for gastroesophageal reflux (GER) in symptomatic adults. Response to this therapy is assessed to confirm the diagnosis of GER, and is often advocated as the best way to establish the causes and effects of the disease. It is well documented that reflux occurs throughout the life span. However, the incidence in children is difficult to estimate, requiring interpretation of behavior and symptoms in nonverbal and atypical presentations. Unfortunately, the diagnosis of GER in children is often made after the development of complications such as aspiration pneumonia, esophagitis, or ulcers. Early recognition and intervention by primary care providers is necessary to prevent such serious complications of untreated GER. This article presents the pathophysiology and clinical manifestations of GER. Diagnosis in children is discussed, and recommendations for empiric therapy, including conservative measures and drug therapies, are presented.     

Contemporary medical therapy for gastroesophageal reflux disease

Gastroesophageal reflux disease is a chronic disorder that requires long-term therapy in most patients. The appropriate medical therapy should be individualized to the severity of symptoms, the degree of esophagitis and the presence of other acid-reflux complications. Lifestyle changes should form the basis of any therapeutic approach. In patients with mild to moderate disease, initial therapy with histamine H2-receptor antagonists in conventional dosages is suggested. Prokinetic agents are potentially useful in patients with impaired esophageal or gastric motor function, but their efficacy as single agents does not appear to surpass that of standard doses of H2 blockers. Sucralfate, a cytoprotective agent, is an additional therapeutic option. For patients with more severe disease, omeprazole and lansoprazole provide unequaled healing rates and accelerated symptom relief. In most patients, maintenance therapy is vital. Surgery is indicated in patients whose disease is refractory to medical therapy and in those who develop complications not amenable to medical therapy.     

Gastroesophageal reflux disease--extraesophageal manifestations

Gastroesophageal reflux is often associated with symptoms of the respiratory tract. Chronic cough of unknown origin, laryngeal complaints and even non allergic asthma, resistant to steroid therapy, are suspicious of being reflux related. These extraesophageal manifestations can occur without typical reflux complaints, such as heartburn, and even without evident esophagitis. Therefore, prolonged pH-monitoring is essential to confirm the diagnosis. In some cases it will be adequate to start a therapeutic trial with proton pump inhibitors (PPI) to prove the causal connection between reflux and symptoms. The treatment of the extraesophageal manifestations of gastroesophageal reflux disease is identical with the management of reflux esophagitis. PPI are the treatment of choice. Sometimes higher doses of PPI are required. Fundoplication may be appropriate for selected patients.     

Reflux esophagitis in children: a scanning and transmission electron microscopy study

In children, excess of gastroesophageal reflux causes lesions of the esophageal mucosa that we have studied by scanning and transmission electron microscopy (SEM and TEM respectively) in 27 grasp biopsies prelevated during endoscopic procedures. Ultrastructural lesions can be graded on the basis of their severity. In grade I, epithelial cells are well preserved in the deepest layers whereas the superficial cells display ultrastructural alterations such as irregular microridges or reduced intercellular junctions. In grade II, the surface is composed of extruding cells and in the intermediate layer, large intercellular spaces containing lympho-monocytic cells are visible. In grade III, the mucosal surface is characterized by crater-like erosions, degenerating cells are visible in all the layers; in two patients columnar epithelium-lined areas (Barrett's esophagus) have been identified. Our results suggest that in patients with reflux esophagitis, ultrastructural examination of grasp biopsies prelevated by pediatric endoscopes allows a grading of the anatomical lesions providing data that can not be obtained by conventional histology.     

Diagnosis and management of urinary tract infections in childhood

The children at greatest risk for kidney damage are infants and young children with febrile urinary tract infection in whom effective treatment is delayed, those with gross vesico-urethral reflux, and those with anatomic or neurogenic urinary tract obstruction. Evaluation and management of pediatric patients with urinary tract infections are summarized.     

Prior childhood sexual abuse in mothers of sexually abused children

OBJECTIVE: To study extensively the therapeutic approach of gastroesophageal reflux disease in intellectually disabled children. DESIGN: We studied the effect of omeprazole sodium on healing and symptom relief in 52 institutionalized intellectually disabled children (male-female, 21:31; mean age, 15.4 years; range, 4-19 years). INTERVENTION: Endoscopically proven esophagitis (grades I-IV, Savary-Miller classification) was treated with omeprazole sodium, 40 mg/d (20 mg/d for children weighing <20 kg) as healing dose for 3 months, and 20 mg/d (10 mg/d for children weighing <20 kg) as maintenance dose for another 3 months. After 3 and 6 months, results of treatment were evaluated using symptom scoring and/or endoscopy. For patients with relapse, the dose was increased. RESULTS: At first endoscopy, 19 patients (36%) of 52 showed grade I esophagitis; 20 (38%), grade II; 6 (12%), grade III; and 7 (13%), grade IV. In 44 (86%) of 51 patients, treatment was effective in healing esophagitis and keeping patients in remission, independent of the severity of esophagitis. In 7 patients (14%), a symptomatic relapse was observed after decreasing the dose. However, these patients became symptom free again after increasing the dose and showed healing on endoscopy at the end of the study. One child did not finish the study for reasons not related to therapy. Marked improvement of persistent vomiting, regurgitation, food refusal, iron deficiency anemia, and signs of depression was seen at the end. CONCLUSIONS: Omeprazole is highly effective for all grades of esophagitis in intellectually disabled children, without adverse effects. The dose needed to maintain the remission can be titrated according to the reflux symptoms. One disadvantage of medical therapy is that it is open ended, in contrast to operation, but surgery in this population has high mortality and complication rates.     

A new surgical management of esophageal stenosis without esophagectomy

In many cases, reflux esophagitis following surgical treatment for esophageal stenosis is caused by the recurrence of that after esophagectomy and esophogogastrostomy. We performed a new management without esophagectomy for a 66-year-old man with sliding hiatal hernia and esophageal stenosis induced by reflux esophagitis. A Expanding Metalic Stent (MES) was inserted to the stenotic portion of the esophagus, and then Collis-Nissen's procedure was done through left thoracotomy and phrenotomy. The postoperative course was satisfactory, and no gastroes-ophageal reflux was detected with the use of 24h pH-monitoring of the esophagus after surgery.     

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids

BACKGROUND: The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. RESULTS: Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.     

Gastroesophageal reflux and airway disease

Gastroesophageal reflux may cause a variety of airway diseases such as asthma, aspiration pneumonia, chronic bronchitis, posterior laryngitis, and ulceration or polyp formation on the vocal cords. Among these asthma seems most common and important clinically. Reflux not only may trigger and aggravate an episode of airway obstruction but also may contribute to nocturnal symptoms. Both clinical and experimental observations suggest that the pathogenetic mechanism may be a vagal reflux following stimulation of lower esophageal receptors and/or microaspiration of gastric acid into the trachea. Diagnosis is usually based on clinical history of asthma and symptoms of gastroesophageal reflux, but in some cases, diagnostic tests such as 24-hour esophageal pH monitoring may be necessary. General measures to avoid reflux and an H2-receptor antagonist together with supportive gastric medications may be the standard treatment. If symptoms persist, proton pump inhibitor may be helpful. Antireflux surgery may provide long-term improvements. Although surgical treatment is indicated only in patients with intractable esophagitis at present, it may be used more commonly through a laparoscopic approach in the near future.     

Parental smoking and infection with Helicobacter pylori among preschool children in southern Germany

BACKGROUND: Endoscopic examination (direct laryngoscopy and bronchoscopy) is the method of choice for diagnosis of respiratory symptoms of unknown cause in children. However, gastroesophageal reflux is being recognized increasingly often as a cause of pediatric respiratory symptoms and is difficult to diagnose on the basis of findings from direct laryngoscopy and bronchoscopy. In cases in which gastroesophageal reflux was included in the differential diagnosis, we additionally performed esophagoscopy with esophageal mucosal biopsies. OBJECTIVES: To determine the feasibility, safety, and efficacy of routinely performing esophageal biopsies during triple endoscopy in children. METHODS: Twenty-four children ranging in age from 2 weeks to 10 years were referred for airway evaluation. Under general anesthesia, children underwent direct laryngoscopy and bronchoscopy and esophagoscopy with mucosal biopsy. RESULTS: Esophageal mucosa biopsy specimens were quickly and safely obtained during endoscopic evaluation. There were no complications. Reflux esophagitis was present in 54% of biopsy specimens, as suggested by basal cell hyperplasia, papillary elongation, and/or inflammatory cell infiltrates. CONCLUSION: Gastroesophageal reflux is often difficult to diagnose in the pediatric population. When direct laryngoscopy and bronchoscopy is performed during examination of the child with airway symptoms, the addition of esophagoscopy with mucosal biopsies will safely and quickly provide data regarding the potential contribution of gastroesophageal reflux.     

Reflux disease: drug treatment

Reflux disease of the esophagus is characterized by a high prevalence and by high relapse rates. Upper endoscopy is the key procedure for diagnosis of the disease as well as for follow up, since treatment is determined by disease intensity as judged by endoscopy. High activity of disease is associated with an increased risk of complications, in the worst case development of adenocarcinoma. General recommandations (weight reduction, change of eating habits) constitute the start of each treatment regimen, and may add to improvement of symptoms, sometimes in combination with antacids. Prokinetics and H2-receptor antagonists are effective in mild reflux disease (grade O, I), but even in these situations proton pump inhibitors (PPI) exhibit better relief of symptoms and more rapid healing. PPI are the drugs of first choice for higher disease activity, often in larger than standard daily doses. The treatment period for acute disease may be as long as 12 weeks. Long term prophylaxis is only effective with PPIs, mostly in the standard daily dose. Duration of long term treatment is determined by disease activity and tendency of the lesions to heal. Today, in case of treatment failure and of high grade lesions antireflux surgery is increasingly being reconsidered, particularly since minimally invasive methods are available.