[The treatment of gastroesophageal reflux disease].
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Algorithms↗
Biomedical subjects
E C Klinkenberg-Knol
Publications and source records attributed to E C Klinkenberg-Knol.
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.
Gastroesophageal Reflux↗
Anorectal function investigations in incontinent and continent patients. Differences and discriminatory value.
Anal manometry, rectal capacity measurement, and the saline-infusion test were performed in 350 patients, 178 of whom had fecal incontinence and 172 of whom were continent. Anal manometry was also performed in 80 control subjects, whose results were compared with the patients. Women and older patients exhibited lower pressures. Compared with continent patients, incontinent patients had lower anal sphincter pressures at rest and during squeeze, a smaller rectal capacity, and leaked earlier and more with the saline infusion test. Differentiation between incontinent and continent patients was not possible with a single test because there was complete overlap. The maximum squeeze pressure showed the best discrimination. Combining the three tests did not show better discrimination than any individual test. Anal pressure and rectal capacity below the normal range only were found in very few incontinent patients. The authors' study demonstrates that no prediction can be made about continence with anorectal function tests. Therefore, in the individual patient, an abnormal result in one test must be interpreted with caution and only in relationship with other tests, especially when therapeutic surgery is considered.
Adult↗
Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis.
Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2-receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia.
Aged↗
Combined gastric and oesophageal 24-hour pH monitoring and oesophageal manometry in patients with reflux disease, resistant to treatment with omeprazole.
Combined oesophageal and gastric 24-hour pH monitoring and oesophageal manometry were performed in 19 patients with resistant reflux oesophagitis after short-term therapy with omeprazole (40 to 60 mg daily) or during maintenance treatment with omeprazole (20 to 80 mg daily). Omeprazole's effects on acidity were analysed as well as any possible influence on oesophageal motility. A pH in the stomach of below 4 was present during considerable periods of time (in 27 of 29 measurements), particularly during the night. As a consequence, pathological gastro-oesophageal reflux occurred, particularly in the supine period. Insufficiency of the lower oesophageal sphincter was present in all but one patient; decreased or virtually absent motility of the oesophagus was found in 63% of the patients. Combined intragastric and intra-oesophageal pH monitoring, with oesophageal manometry, may contribute to the management of patients with reflux disease resistant to treatment with omeprazole. The present study emphasizes the need to individualize therapy in patients with refractory gastrooesophageal reflux disease.
Adult↗
Temporary cessation of long-term maintenance treatment with omeprazole in patients with H2-receptor-antagonist-resistant reflux oesophagitis. Effects on symptoms, endoscopy, serum gastrin, and gastric acid output.
To study the effects of sudden withdrawal of long-term maintenance therapy with omeprazole for up to 4 years, 14 patients with resistant reflux oesophagitis were asked to stop their treatment temporarily. Ten days after withdrawal median basal acid output had increased significantly (p = 0.01) from 0 (range, 0-1.18) on day 1 to 1.95 (range, 0-8.45) mmol/h on day 10. Median serum gastrin levels were raised during treatment with omeprazole but decreased significantly from 166 to 42 ng/l within the 10 days of the study (p = 0.01). The median integrated gastrin response after meal stimulation decreased significantly (p less than 0.001) from 758.6 ng/l on day 1 to 267.9 ng/l on day 10. On day 10 after withdrawal of omeprazole all patients had endoscopic and symptomatic evidence of recurrent oesophagitis. Reflux patients receiving maintenance treatment with omeprazole for up to 4 years showed prompt normalization of serum gastrin levels and return of gastric acid production within 10 days after stopping the treatment. Consequently, there was a fast recurrence of aggravation of reflux symptoms and oesophagitis.
Adult↗
Soiling: anorectal function and results of treatment.
Forty-five patients with soiling but without faecal incontinence were evaluated by means of anorectal function investigations (anal manometry, rectal capacity and saline infusion test). The causes of soiling and the effect of treatment on both soiling and anorectal function were studied. The results were compared with a control group of 161 patients without soiling or incontinence. The diagnoses were haemorrhoids (10), mucosal prolapse (7), rectal prolapse (6), fistulae (5), proctitis (3), faecal impaction (2), rectocele with intussusception (2), scars after fistulectomy (2) and others (8). Simple inspection and proctoscopy were generally sufficient to establish a diagnosis. For two patients the diagnosis rectocele was made after defaecography. Anorectal test results did not differ between the soiling and control group, did not contribute to establish a diagnosis and did not change after treatment. Only patients with a rectal prolapse had abnormal results in anorectal function tests: a low basal sphincter pressure and a limited continence reserve. Appropriate therapy resulted in complete recovery (44%) or improvement of symptoms (29%).
Anal Canal↗
Management of gastro-oesophageal reflux disease. Are there alternatives to omeprazole?
Several studies have clearly demonstrated that omeprazole is highly efficacious in the management of patients with gastro-oesophageal reflux disease. In particular, wherever H2-receptor antagonists fail to produce results--in patients with severe disease--omeprazole has been shown to be of major value. However, new alternatives are forthcoming; a new generation of more potent H2-receptor antagonists will be available, while 24 pH studies with high-dose ranitidine have shown that acid reflux is suppressed more efficiently than with standard doses. The prokinetic drug cisapride appears to be of importance, not only in the management of patients with mild reflux disease, but also of cases with severe disease when cisapride is combined with a H2-receptor antagonist. Such a combination could also be of value as an alternative to omeprazole in long-term therapy, since it has not yet been shown that indefinite treatment with omeprazole of patients with reflux disease will be safe. In addition, the value of long-term sucralfate, effective in short-term therapy, needs to be evaluated in patients with chronic reflux disease who will not be operated. In forthcoming studies, it will be advisable to incorporate 24-hour pH measurements to detect periods of nonacid suppression more accurately. The future of medical management of gastro-oesophageal reflux disease appears to be promising.
Cisapride↗
Treatment of reflux oesophagitis resistant to H2-receptor antagonists.
Results of medical therapy of reflux oesophagitis are disappointing, especially compared to the success obtained in peptic ulcer disease. H2-receptor antagonists, with or without the addition of mucosaprotectiva or prokinetica, produce healing only in 50% of the patients. Nowadays, even severe, resistant reflux oesophagitis can be treated successfully with the H+/K+-adenosine triphosphatase antagonist omeprazole. Experience of more than 3 years of continuous treatment with omeprazole, in doses which have been adjusted to prevent recurrences, has also demonstrated its high efficacy in the long-term management of the patients. The use of this drug emphasizes the importance of long-standing, strong acid inhibition for this condition, although careful surveillance of the safety profile of this drug remains obligatory.
Drug Administration Schedule↗
Use of omeprazole in the management of reflux oesophagitis resistant to H2-receptor antagonists.
Severe reflux oesophagitis, which is resistant to treatment with high doses of H2-receptor antagonists, can be treated successfully with the H+,K+-ATPase inhibitor omeprazole. Experience from more than 3 years of continuous treatment with omeprazole, in doses adjusted to prevent recurrences, has demonstrated its high efficacy in the long-term management of the patients. The use of this drug emphasizes the importance of long-standing, effective, 24-hour acid inhibition for reflux oesophagitis. Fasting gastrin levels increase 2-fold during the initial treatment period but continued treatment does not induce any further elevation. Omeprazole does not induce pathological changes in the endocrine cell population of the gastric oxyntic mucosa, though in some patients an increase in the argyrophilic cell volume density during omeprazole treatment has been reported. Careful surveillance of the safety profile of this drug is continuing.
Esophagitis, Peptic↗
Twenty-four-hour ambulatory oesophageal pH monitoring: experience in The Netherlands.
Twenty-four-hour ambulatory oesophageal pH monitoring has become a major diagnostic method for the evaluation of gastro-oesophageal reflux disease. Essential requirements for registration and reproduction of the pH are reliable pH electrodes, well-performed calibration and optimal reproduction and analysis of the signal. The most commonly used pH probes in The Netherlands are not-combined monocrystalline antimony electrodes (Synectics Ltd, Sweden) and combined glass electrodes (Ingold and Radiometer). For diagnostic intra-oesophageal pH measurements both types are suitable; for research purposes, especially intragastric, glass electrodes are preferable. In The Netherlands several types of solid-state recorders are commercially available: all fulfill the conditions necessary to produce reliable registrations. In the present study, available measuring systems in The Netherlands and current practices associated with ambulatory pH monitoring were evaluated. Inquiry among the Dutch pH registration centres showed that more than half were using Synectics electrodes and equipment. Positioning of the pH probe was based on manometry (25%), fluoroscopy (22%) or endoscopy (20%). In the initial phase there were many problems, especially related to ignorance of the complicated registration procedure. For ambulatory pH measurements we recommend a simple datalogger with a sufficient memory capacity and direct interface with a PC, a combined glass electrode positioned 5 cm above the manometrically determined lower oesophageal sphincter. For clinical interpretation of the results the percentage of time with pH below 4 is probably the most reliable parameter for the detection of pathological gastrooesophageal reflux.
Calibration↗
[Fecal soiling: a painful problem].
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Adolescent↗
Investigation of anorectal function.
Anorectal function tests were performed in 280 consecutive patients, who were referred for evaluation of different anorectal disorders. The relationship between the estimated anal sphincter pressure on digital palpation and the measured pressure on anal manometry was investigated and the interrelationship between anal manometry, rectal capacity and the saline infusion test was defined. A significant correlation (P less than 0.001) was found between digitally and manometrically measured anal sphincter pressure. Considering the relationship between the three specific anorectal function tests, only manometry and the saline infusion test correlated to some extent (P less than 0.01). This study shows that digital palpation is helpful in anorectal function investigation, but to establish the exact anal pressures, anal manometry is mandatory. Furthermore, the poor correlation observed indicates that single tests represent different aspects of anorectal function and therefore they need to be performed together.
Adolescent↗
The effects of omeprazole and ranitidine on 24-hour pH in the distal oesophagus of patients with reflux oesophagitis.
Ambulatory 24-h pH monitoring in the distal oesophagus was performed in seven patients with erosive or ulcerative reflux oesophagitis to compare the effects of omeprazole and ranitidine in the management of gastro-oesophageal reflux disease. In a double-blind, crossover study patients were treated with either 60 mg o.m. omeprazole or 150 mg b.d. ranitidine. The pH measurements were performed before treatment and on the fourteenth day of treatment with either regimen. The total acid exposure time (percentage total time pH less than 4) was abnormal in six out of seven patients before treatment. During treatment with omeprazole the acid exposure time of five patients was normal in comparison with only two patients during ranitidine therapy. However, even with a rather high dose of omeprazole, pathological gastro-oesophageal reflux may still occur.
Adult↗
Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus.
The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.
Aged↗
Treatment of reflux oesophagitis with H2-receptor antagonists.
The important therapeutic value of H2-receptor antagonists for the treatment of patients with reflux oesophagitis has been demonstrated beyond doubt. A large number of patients have been treated with cimetidine or ranitidine in controlled as well as open short-term studies. Mild to moderately severe reflux oesophagitis heals effectively when H2-receptor antagonists are prescribed for a sufficient time period, preferentially 12 weeks. The more severe forms of oesophagitis, however, need more profound acid suppression, with potent H2-receptor antagonists, addition of prokinetic agents, or treatment with H+/K+ATP-ase antagonists. Omerpazole has proven to be of high efficacy, particularly in the management of severe reflux oesophagitis. Data on long-term treatment with H2-receptor antagonists, to prevent recurrences after healing, are not reassuring: long-term low-dose H2-receptor antagonist therapy is not effective, and trials should be undertaken with higher doses of H2-receptor antagonists, more potent antagonists, or with combinations of antagonists and prokinetics. In these studies, 24-h intraoesophageal and intragastric pH measurements should be incorporated, to detect more accurately time periods of nonsuppressed acid secretion. Such studies will undoubtedly better define the therapeutic place of the presently available and forthcoming H2-receptor antagonists.
Anti-Ulcer Agents↗
Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis.
Omeprazole 60 mg once daily was compared with ranitidine 150 mg twice daily in an endoscopically-controlled, double-blind randomised trial in 51 outpatients with erosive or ulcerative reflux oesophagitis (grade 2 or 3). Endoscopy was repeated after 4 weeks and, in the absence of healing, again after 8 weeks. Symptoms were assessed before entry and after 2, 4, and 8 weeks. Patients who were unhealed after 8 weeks were blindly switched to the other drug and treatment was continued for another 4 to 8 weeks. The healing rate (change to grade 0 or 1 oesophagitis) after 4 weeks was 19 of 25 patients treated with omeprazole and 7 of 26 patients treated with ranitidine (p = 0.002). The corresponding figures after 8 weeks were 22 of 25 and 10 of 26 (p = 0.001). The higher healing rate with omeprazole was reflected in a significantly faster and stronger improvement of reflux symptoms. 13 patients, who were unhealed after 8 weeks on ranitidine, were healed after switching treatment. Healing was achieved in 1 of 3 patients who were switched to ranitidine. There were no adverse events or changes in laboratory variables of clinical importance. Omeprazole is superior to ranitidine in the short-term treatment of reflux oesophagitis.
Clinical Trials as Topic↗