Severe Reflux Esophagitis Research Articles

Declined human esophageal mucin secretion in patients with severe reflux esophagitis.

It has been recently demonstrated that human esophageal submucosal mucous glands exhibit the ability to secrete copious amounts of mucin, well known within the gastrointestinal tract for its protective quality against hydrogen ion and pepsin. Since mucin may also play a protective role within the esophageal compartment, we have studied the rate of secretion of esophageal mucin in patients with RE. Mucin was assessed by periodic acid-Schiff methodology in esophageal secretion collected during continuous perfusion with saline (period I) followed by HCl (period II), HCl/pepsin (period III), and final saline (period IV), mimicking the natural gastroesophageal scenario. The basal rate of the luminal release of mucin in patients with grade II RE was 18% lower as compared with controls. During exposure of the esophageal mucosa to an HCl/pepsin solution, esophageal mucin output in the RE group was 52% lower than in the control group (0.154 +/- 0.027 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.025). Furthermore, the rates of esophageal mucin output in patients with grade III RE during esophageal perfusion with saline and HCl/pepsin were 62% (0.090 +/- 0.021 vs 0.239 +/- 0.036 mg/cm2/min; P = 0.016) and 86% (0.048 +/- 0.010 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.001) lower when compared with corresponding values in controls. After endoscopic healing of RE, the overall impairment in the rate of esophageal mucin secretion in patients with grade II improved from 31% to 17% at the end of therapy, whereas in patients with grade III the impairment in mucin secretion improved only marginally from 71% to 69%.(ABSTRACT TRUNCATED AT 250 WORDS)

Omeprazole. An update of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole, a gastric acid pump inhibitor, dose-dependently controls gastric acid secretion: the drug has greater antisecretory activity than histamine H2-receptor antagonists. Omeprazole 20 to 40 mg/day is more effective than histamine H2-receptor antagonists in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. Available data suggest that omeprazole 10 to 40 mg/day is also more effective than ranitidine in the maintenance therapy of duodenal ulcer and reflux oesophagitis. The drug is also effective in patients with duodenal ulcer, gastric ulcer or reflux oesophagitis poorly responsive to histamine H2-receptor antagonists. The efficacy of omeprazole 20 mg/day appears to be similar to that of lansoprazole 30 mg/day in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. However, most available studies have been reported in abstract form only, and 2 of 3 studies in patients with duodenal ulcer have shown greater healing rates at 2 (but not 4) weeks with lansoprazole. Helicobacter pylori eradication decreases duodenal ulcer relapse rates and appears to be associated with improved duodenal ulcer healing rates. Evidence also suggests that H. pylori eradication is associated with reduced gastric ulcer relapse rates. Omeprazole monotherapy may suppress but does not eradicate H. pylori infection. Eradication rates with omeprazole 20 or 40 mg twice daily plus amoxicillin usually up to 2 g/day (3 g/day in a few studies) for 2 weeks appear to be similar to those of standard triple therapy (bismuth salt plus metronidazole, plus tetracycline or amoxicillin) or omeprazole plus clarithromycin, although eradication rates vary widely. Omeprazole plus amoxicillin appears to be better tolerated than triple therapy and represents a first-line treatment alternative in patients with H. pylori-associated peptic ulcer disease. Omeprazole plus amoxicillin plus metronidazole appears to be more effective than omeprazole plus amoxicillin in patients with metronidazole-sensitive H. pylori infection. Omeprazole remains a treatment of choice in patients with Zollinger-Ellison syndrome. The dosages should be adjusted according to individual response. However, relatively low dosages of 10 to 40 mg/day may be sufficient in some patients. The drug has also shown promise in the treatment of children with severe reflux oesophagitis, in patients with reflux oesophagitis and coexisting systemic sclerosis, and in the prevention of aspiration pneumonia. Evidence suggests that omeprazole is more effective than ranitidine in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage who continue to take NSAIDs, especially in patients with large gastric ulcers; however, completion of ongoing studies is required to verify this.(ABSTRACT TRUNCATED AT 400 WORDS)

Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis.

Thirty two consecutive patients (age range 6 months-13.4 years) with severe reflux oesophagitis were randomised to a therapeutic trial for eight weeks during which they received either standard doses of omeprazole (40 mg/day/1.73 m2 surface area) or high doses of ranitidine (20 mg/kg/day). Twenty five patients completed the trial (12 on omeprazole, 13 on ranitidine). At entry and at the end of the trial patients underwent symptomatic score assessment, endoscopic and histological evaluation of the oesophagus, and simultaneous oesophageal and gastric pH measurement; results are given as median (range). Both therapeutic regimens were effective in decreasing clinical score (omeprazole before 24.0 (15-33), after 9.0 (0-18); ranitidine before 19.5 (12-33), after 9.0 (6-12)), in improving the histological degree of oesophagitis (omeprazole before 8.0 (6-10), after 2.0 (0-60); ranitidine before 8.0 (8-10), after 2.0 (2-6), and in reducing oesophageal acid exposure, measured as minutes of reflux at 24 hour pH monitoring (omeprazole before 129.4 (84-217), after 44.6 (0.16-128); ranitidine before 207.3 (66-306), after 58.4 (32-128)) as well as intragastric acidity, measured as median intragastric pH (omeprazole before 2.1 (1.0-3.0), after 5.1 (2.2-7.4); ranitidine before 1.9 (1.6-4), after 3.4 (2.3-5.3)). Serum gastrin concentration was > 150 ng/l in four patients on omeprazole and in three patients on ranitidine. It is concluded that in children with refractory reflux oesophagitis high doses of ranitidine are comparable with omeprazole for the healing of oesophagitis and relief of symptoms; both drugs resulted in efficacious reduction of intragastric acidity and intra-oesophageal acid exposure.

Histologic grading of reflux oesophagitis and its relationship with intra-oesophageal and intragastric pH variables

Objective To determine the relationship between histologic grading of reflux oesophagitis and both intra-oesophageal acid exposure and intragastric acidity. Methods Endoscopy and simultaneous 24-h recording of intra-oesophageal and intragastric pH. Patients Eighty-one patients with symptoms strongly suggesting gastro-oesophageal reflux disease; intra-oesophageal and intragastric pH was also recorded in 16 controls. Results: Reflux oesophagitis was found in 71 patients and was graded as follows: mild-A (15 patients), mild-B (26 patients), moderate (16 patients) and severe (14 patients). Abnormal gastro-oesophageal reflux was found in the remaining 10 patients, although there was no histological evidence of reflux oesophagitis. There was no statistical difference in the oesophageal acid exposure or in the number of gastro-oesophageal reflux episodes lasting ≥5 min when the reflux oesophagitis groups were compared. Intragastric acidity, median intragastric pH and percentage of intragastric pH <2 were significantly higher in patients with severe reflux oesophagitis compared with the other reflux oesophagitis groups. Conclusions Endoscopy and histology of the oesophagus seem to be the most valuable diagnostic tools in children with symptoms suggesting gastro-oesophageal reflux disease. Furthermore, the severity of oesophagitis appears to be related more to the potency of refluxed material than to oesophageal acid exposure.

Prolonged clearance is the primary abnormal reflux parameter in patients with progressive systemic sclerosis and esophagitis.

The purpose of this study is to determine if frequent reflux events from an incompetent LES or poor clearance from decreased peristalsis is the predominant abnormality in PSS patients with severe reflux esophagitis. Seven patients with both classic manometric findings of PSS and endoscopic findings of esophageal ulcerations and/or Barrett's esophagus were compared to nine patients with similar endoscopic findings but with no evidence of a connective tissue disorder. All patients underwent simultaneous intraesophageal pH monitoring and scintigraphy for a total of 40 min after a radiolabeled meal. Four of the PSS patients and all the non-PSS patients had simultaneous manometry. We found that PSS patients had significantly fewer reflux events (P less than 0.01), but the reflux events had significantly longer duration (P less than 0.01) compared to patients with similar severity of esophagitis and no connective tissue disease. We conclude that decreased smooth muscle peristalsis appears to be the primary contributor to acid exposure and esophageal injury in PSS.

Vicryl-scarf-induced scarring around esophagogastric junction as treatment of esophageal reflux disease. An experimental study in the dog.

A ringlike structure around the cardia has proven to be sufficient in preventing gastroesophageal reflux, as seen with the Angelchick prosthesis. To avoid the insertion of a nonabsorbable foreign body, a scarring was induced by implanting a Vicryl scarf around the esophagogastric junction. Reflux disease was induced in 18 dogs by circular cardiomyomectomy. In 12 dogs, a Vicryl scarf was laid around the cardia; six dogs served as controls. All of the dogs in the control group either died or had to be sacrificed due to severe reflux esophagitis. All animals receiving the scarf survived the entire duration of the experiment. Endoscopically, only one case of temporary reflux esophagitis could be detected. Long-term pH-metry demonstrated complete reflux suppression after the third postoperative month. Radiographically, esophagogastric transit was always unimpaired. On autopsy, the scarf was found to have changed into a slim scarring after the sixth postoperative month and then remained unaltered. We conclude that inducing scarring around the cardia is as effective in reflux prevention as the silicone ring.

Gastroesophageal reflux after endoscopic injection sclerotherapy.

The effect of sclerotherapy of esophageal varices on the gastroesophageal reflux was studied. Gastroesophageal reflux was monitored by a 24-h pH-monitoring catheter introduced into the distal esophagus. The results of pH monitoring of 16 patients who underwent sclerotherapy were compared with those of 21 patients with untreated varices. Seven of the 16 treated patients showed high occurrence rates of gastroesophageal reflux comparable to those observed in cases with severe reflux esophagitis. In the untreated group, only one patient showed pathological reflux (there was a significant difference between treated and untreated groups; p less than 0.01). When the level of reflux was compared with factors that might influence sclerotherapy-induced gastroesophageal reflux, there was a positive correlation between the magnitude of reflux and amount of sclerosant injected paravariceally in the submucosal tissue (p less than 0.05). The results indicate that the paravariceal injection of sclerosant for the treatment of esophageal varix may cause pathological gastroesophageal reflux after sclerotherapy is completed.

Severe Reflux Esophagitis After Vertical Banded Gastroplasty for Treatment of Morbid Obesity

Herein we describe two patients with medically refractory, severe reflux esophagitis after vertical banded gastroplasty for morbid obesity. Neither patient had symptoms of reflux preoperatively. Both patients underwent conversion to a vertical Roux-en-Y gastric bypass, an operation that prevents acid and peptic reflux and maintains a weight-reducing anatomy. Symptoms of gastroesophageal reflux are common (they occur in approximately 38% of patients) after vertical banded gastroplasty has been performed. Patients with unusually severe reflux may require operative management.

Omeprazole

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis

To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance.

Long-term maintenance treatment of reflux esophagitis with omeprazole

Thirty-four patients with H2-blocker-resistant reflux esophagitis subsequently healed by 40 mg omeprazole daily entered a maintenance study with 20 mg omeprazole. In 31 evaluable cases the observation period was at least 12 months (mean 24 months). Esophagitis remained in remission in two thirds of patients despite dose reduction. Relapses of esophagitis occurred in 10 cases within six months, which rapidly healed by increasing the omeprazole dose to 40 mg. No further recurrence with 20 mg omeprazole was found later than six months. Peptic strictures primarily requiring repeated dilatation in six patients during healing with omeprazole did not reappear while on omeprazole maintenance. Major side effects that could be attributed to omeprazole were not observed. Gastrin levels remained within or slightly above the normal range in the vast majority. It is concluded that omeprazole maintenance treatment in severe reflux esophagitis is an effective and safe therapy.

Recent Advances in the Management of Gastro-Oesophageal Reflux Disease

The basis of treatment of reflux oesophagitis is change in behaviour and lifestyle. In the presence of mild symptoms antacids/alginate may be instituted. In case of Savary grade I and II oesophagitis at endoscopy, H2-receptor antagonists (H2RAs), alone or in combination with a prokinetic or mucosaprotective agent, are the first choice of treatment. Drug treatment should be continued for at least 8-12 weeks. In case of resistance to treatment or in case of severe and/or complicated reflux oesophagitis, omeprazole should be prescribed. Maintenance treatment is necessary in patients with severe reflux oesophagitis and in patients with quick relapses, once therapy has stopped. Full-dose H2RAs are required to prevent recurrences. In case of resistance to H2RAs, omeprazole should be used. Anti-reflux surgery should be considered in patients, especially at young age, who have an insufficient response to medical management, due either to lack of compliance or to therapeutic failure.

Prospective evaluation of omeprazole treatment in reflux oesophagitis refractory to H2‐receptor antagonists

The efficacy of omeprazole therapy (40 mg daily) in H2-blocker refractory severe reflux oesophagitis (Grade II-IV; Savary and Miller classification) was investigated in 61 patients. Mean duration of reflux disease and preceding H2-antagonist treatment were 4.3 years and 15 months, respectively. Healing rates at 4, 8 and 12 weeks were 48%, 80% and 92%, respectively. There was a correlation between severity of oesophagitis and duration of omeprazole therapy necessary for healing. Three patients (5%) required higher dosages than 40 mg for healing. Symptomatic responses paralleled healing. It is concluded that omeprazole is a highly effective drug for severe reflux oesophagitis not responding to H2-blocker treatment and that 40 mg daily is the optimal dose.

Omeprazole in H2 Receptor Antagonist-Resistant Reflux Esophagitis

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.

Recent Studies of the Pathophysiology and Diagnosis of Esophageal Symptoms

The three main symptoms of esophageal disease or disorder are dysphagia, chest pain, and heartburn. Dysphagia in achalasia is mainly due to a non-relaxing lower esophageal sphincter (LES). The mechanism of dysphagia in diffuse esophageal spasm and related motor disorders is related to a combination of several factors including incomplete LES relaxation, failed or weak peristalsis (pressure less than 30 mmHg in the distal esophagus, and orad positive pressure gradient). Meal manometry and balloon distention may prove to be useful provocation tests. Chest pain of esophageal origin may be due to gastroesophageal reflux and esophageal motility disorders; it may also be a manifestation of an irritable esophagus, in which the esophagus is hypersensitive to various stimuli (chemical, mechanical, ischemic). Esophageal provocation tests may suggest the esophageal origin of the pain but do not give information on the nature of the esophageal disorder. Twenty-four-hour pH and pressure measurements may, however, yield this information. Heartburn and acid regurgitations are the most typical symptoms of gastroesophageal reflux. Transient relaxations of the LES are considered to be an important contributory mechanism of reflux. Absent basal LES pressure is another mechanism, which accounts for about one-fourth of the reflux episodes in patients with severe reflux esophagitis. During long-lasting inappropriate relaxations, swallows often produce deglutitive contraction waves that die out in the upper esophagus, suggesting that reflux often occurs during periods of inhibition of both LES tone and peristaltic esophageal activity.

Acute treatment of reflux oesophagitis: a multicentre trial to compare 150 mg ranitidine b.d. with 300 mg ranitidine q.d.s.

H2-receptor antagonists administered in conventional dosage regimens fail to heal a significant proportion of patients with moderate or severe reflux oesophagitis. We have compared the effects of a higher dose of ranitidine (300 mg q.d.s.) with the currently recommended dosage regimen (150 mg b.d.) in 138 patients suffering from reflux oesophagitis. After 4 weeks of treatment 29% of patients who received 150 mg ranitidine b.d., and 63% of patients who received 300 mg ranitidine q.d.s. had complete endoscopic healing of their lesions (P less than 0.0001). After 8 weeks these proportions had increased to 54% and 75%, respectively (P less than 0.01). After 4 weeks of treatment, compete symptomatic relief had been achieved in 46% of patients who received 150 mg ranitidine b.d. and in 67% of patients who received 300 mg ranitidine q.d.s. (P less than 0.05). After 8 weeks these proportions were 64% and 84%, respectively (P less than 0.05). Both dosage schedules were well-tolerated. We conclude that more rapid symptom relief and healing in reflux oesophagitis can be achieved with 300 mg ranitidine q.d.s. than with 150 mg ranitidine b.d.

Therapeutic Options in Severe Reflux Oesophagitis

Standard doses of H2-receptor antagonists are usually effective in milder forms of reflux oesophagitis, but these lower doses induce relatively low healing rates in more severe forms of the disease. In the patients with severe reflux oesophagitis, prokinetic or mucosa-protecting agents do not offer better results, whereas a combination of standard doses of H2-receptor antagonists with prokinetic or mucosa-protecting agents results in no or only marginally better results than obtained with H2-receptor antagonist mono-therapy. Several studies have shown that insufficient inhibition of gastric acid secretion is the major reason for the low healing rates obtained with standard doses of H2-receptor antagonists. It has recently been shown that higher doses of ranitidine increase the time the oesophageal pH is above 4 and induce higher healing rates in patients with severe reflux oesophagitis. Therefore, we now have three therapeutic options for patients with severe reflux oesophagitis: first, higher doses of hi...

Efficacy of sucralfate in refractory reflux esophagitis. Results of a pilot study.

Patients with severe reflux esophagitis unresponsive to standard medical therapy constitute a vexing clinical problem. We evaluated 8 patients with long-standing gastroesophageal reflux disease complicated by peptic stricture (n = 6), Barrett's esophagus (n = 5), bleeding esophageal ulcer (n = 2), and/or failure or prior antireflux surgery (n = 4), and 4 patients with rapidly advancing esophagitis following surgical resection of the cardia. After an 8-week course of full-dose H2-receptor antagonists, domperidone and antacids, marginal clinical improvement and unchanged or worsened endoscopic appearance of esophagitis was observed in all patients. Thereafter, in an attempt to enhance esophageal mucosal resistance, sucralfate alone (4.0 g/d) was given for 8 weeks. Both symptoms and endoscopic appearance improved in all patients after sucralfate, and the need for dilatation of strictures was lessened. On follow-up, complete healing of esophagitis was demonstrated by endoscopy in 6 patients after 4 to 6 months of uninterrupted sucralfate therapy. The results of this pilot study indicate that (cyto)protection with sucralfate has an important therapeutic potential in reflux esophagitis. They also suggest that impaired esophageal epithelial resistance is an important pathophysiological factor in persistence of esophageal inflammation in esophagitis refractory to conventional treatment.

Barrettʼs Esophagus in an Infant

Data on the frequency of regression of Barrett's esophagus after medical therapy or antireflux surgery in adult patients are conflicting; these data, with regard to pediatric age, where Barrett's esophagus is considered rare, are scarce and disappointing after antireflux surgery. We report a 4-month-old infant affected by severe reflux esophagitis who developed a junctional-type Barrett's epithelium. Histochemical procedures to detect mucin pattern were also carried out. The regression of Barrett's esophagus was observed 4 months after antireflux surgery whereas medical therapy had been unsuccessful. We suggest that esophageal biopsy should also be performed in the presence of severe esophagitis. Longer follow-up observations of other patients may clarify the role of antireflux surgery when Barrett's esophagus complicates gastroesophageal reflux (GER).

Barrett's Esophagus in an Infant

Summary:Data on the frequency of regression of Barrett's esophagus after medical therapy or antireflux surgery in adult patients are conflicting; these data, with regard to Pediatric age, where Barrett's esophagus is considered rare, are scarce and disappointing after antireflux surgery. We report a 4‐month‐old infant affected by severe reflux esophagitis who developed a junctional‐type Barrett's epithelium. Histochemical procedures to detect mucin pattern were also carried out. The regression of Barrett's esophagus was observed 4 months after antire‐flux surgery whereas medical therapy had been unsuccessful. We suggest that esophageal biopsy should also be performed in the presence of severe esophagitis. Longer follow‐up observations of other patients may clarify the role of antireflux surgery when Barrett's esophagus complicates gastroesophageal reflux (GER).