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GASTROESOPHAGEAL REFLUX DISEASE: DIAGNOSIS AND TREATMENT |
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(from the conclusions of the Consensus Conference organized by the French National Society of Gastroenterology and the Belgian Royal Society of Gastroenterology, January 1999) J Marescaux , MD , FRCS , Hôpitaux Universitaires de Strasbourg, Strasbourg, France |
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1. Introduction 2. Diagnosing GERD 3. Assessing GERD 4. Medical therapy 5. Therapeutic strategy 6. Surgical therapy 7. References |
1.
Introduction/pathophysiology
Gastroesophageal reflux disease (GERD) occurs when part of the gastric contents regurgitates into the esophagus. In clinical terms, it refers to a recurrent
ailment characterized by symptoms and/or esophageal lesions related to this reflux. Esophageal mucosal injury is known as reflux esophagitis (peptic esophagitis).
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1. Introduction 2. Diagnosing GERD 3. Assessing GERD 4. Medical therapy 5. Therapeutic strategy 6. Surgical therapy 7. References |
2.
Diagnosing GERD
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;) Figure 2.2.3.a |
;) Figure 2.2.3.b |
;) Figure 2.2.3.c |
No consensual classification on esophagitis grading has been thoroughly validated. Considering the 3 classifications above, it is crucial to distinguish mild esophagitis (loss of isolated or multiple non-circumferential mucosa[s]), severe esophagitis (loss of circumferential mucosa) and complicated esophagitis (stenoses, ulcers, Barrett’s esophagus). Nevertheless, a normal endoscopy does not rule out the diagnosis of GERD since esophagitis is only manifest in 30% to 50% of cases.
2.3. Diagnosis criteria and pH monitoring
Most often performed in an outpatient setting, 24-hour esophageal pH monitoring is useful in individuals who present with atypical symptoms and normal esophageal mucosa during the endoscopic examination. This test must be performed after discontinuing the antisecretory treatment (1 week for PPIs): it aims at assessing the correlation between symptoms and reflux. Its sensitivity varies from 70% to 90% and its specificity from 85% to 90%. This test has no diagnostic value in patients presenting with esophagitis or typical GERD symptoms (except in some cases of resistance to treatment). Biliary reflux cannot be diagnosed with this test.2.4. Other exams
All other types of exams are rarely needed to establish the initial diagnostic strategy for GERD.-
X-ray contrast swallow is not sufficient.
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Esophageal manometry is not a diagnosis-related examination.
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Measurement of acid gastric secretion and measurement of gastrin level have no practical interest except in some exceptional cases where a gastrinoma is suspected.
2.5. Diagnostic strategy
We propose the following recommendations:1. Typical symptoms without signs of distress occurring in individuals under 50: medical treatment should always be initially prescribed, without systematically resorting to the use of complementary exams. Resistance to medical treatment or early symptom recurrence after discontinuing the treatment is an indication for endoscopic examination.
2. Typical symptoms with signs of distress or in individuals over 50: upper gastrointestinal endoscopy.
3. Atypical digestive or extra-gastrointestinal symptoms: upper gastrointestinal endoscopic examination combined with esophageal pH monitoring if the patient does not have esophagitis.
;) Figure 2.5 |
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Table 2.5 : Physical examination and indications for endoscopy in adults.
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1. Introduction
2. Diagnosing GERD
3. Assessing GERD
4. Medical therapy
5. Therapeutic strategy
6. Surgical therapy
7. References
3.
Assessing the GERD severity level: therapeutic objectives
Classically, esophagitis has been the main criterion in assessing the severity of GERD and its response to therapy. However, in most cases, GERD is a benign functional pathology that does not result in severe lesions. It mainly generates symptoms that may have a negative impact on the quality of life. The severity of symptoms, defined by their intensity and frequency, is not related to the presence or to the intensity of esophagitis.3.1. Evaluation of symptoms and their impact on the quality of life
The negative impact of reflux symptoms on the quality of patients’ lives has been amply demonstrated.Hence, we consider symptoms and quality of life to be the main criterion in assessing the severity of GERD as well as the effectiveness of therapy. Patients must fill in standardized, validated evaluation questionnaires on symptoms and quality of life.
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Document 3.1
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3.2. Natural history of GERD and its complications
The natural history of GERD is often that of a chronic affliciton. Approximately two thirds of patients require intermittent or continuous treatment after several years of follow-up. It is not possible to predict the persistence of symptoms in each individual patient.In most cases, esophagitis lesions are not severe. They are not related to symptom intensity and they rarely worsen during their evolution. The severity of GERD cannot be assessed by these lesions. It is not recommended to attempt to control the healing of these mild esophagitis lesions or to monitor them by repeated endoscopic examinations.
In a minority of cases, especially in individuals over 60, severe esophagitis occurs. Such severe lesions may be a predictive factor of difficult healing, recurrence and complications. An endoscopic monitoring of the healing process is justified and recommended.
The 2 main complications of GERD are peptic stricture and Barrett’s esophagus.
- Peptic stricture is rare (about 1% of cases).
- It is necessary at this point to further describe Barrett’s esophagus because of the risk of carcinoma it entails.
Present in 5% to 10% of patients undergoing endoscopy to assess GERD, Barrett’s esophagus is a condition in which the squamous epithelium of the distal esophagus is replaced by a columnar metaplastic epithelium of fundic (gastric), cardial (junction) or intestinal (specialized) type.
Diagnosis of Barrett’s esophagus is usually established when at least 3 cm of the esophagus is affected. More limited presentations, such as short Barrett’s esophagus, are frequent. The diagnosis of intestinal metaplasia carries a 30-40 fold increased risk for the development of esophageal adenocarcinoma as compared to the normal population. It is believed that malignant degeneration follows the sequence of metaplasia to dysplasia, which then may develop into cancer. Barrett’s esophagus with intestinal metaplasia must be monitored by endoscopy and multiple biopsies. Once the diagnosis of Barrett’s esophagus is confirmed, definitive treatment of the reflux by surgical intervention is recommended. Thereafter, a thorough check-up is recommended every year for patients whose life expectancy and co-morbidity are compatible with a therapeutic treatment for severe dysplasia or cancer ( Falk 2002; Shaheen and Ransohoff; 2002; Spechler, 2002; Incarbone et al ., 2002 ).
The objectives of GERD treatment (medical or surgical) are the following:
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relieving symptoms and allowing a quick return to normal life (in all cases);
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healing of lesions (only in cases of severe or complicated esophagitis);
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prevention of recurrence (in symptomatic cases with frequent relapses and severe or complicated esophagitis).
1. Introduction
2. Diagnosing GERD
3. Assessing GERD
4. Medical therapy
5. Therapeutic strategy
6. Surgical therapy
7. References
4.
Medical therapy
The medications available for the treatment of GERD belong to several therapeutic classes whose efficacy has been well documented. Some of these medications are very effective, although none can permanently cure the disease or prevent recurrence after discontinuing treatment.4.1. Lifestyle modifications
Of the numerous dietary and postural measures commonly recommended, the only one that has proven to be modestly effective is for patients to sleep with their upper bodies in an elevated position. Other measures (stopping smoking and alcohol intake, losing weight, being on a low-fat diet, etc.) are general recommendations that aim at improving the patient's health and have no direct effect on GERD whatsoever.Medications that have been blamed (essentially for pharmacological reasons) for contributing to reflux have, in fact, little effect on the symptoms of GERD. They can therefore be administered when needed. This applies in particular to bronchodilators (theophyllines and beta-2 agonists and contraceptive pills.
4.2. Topics
Controlled studies have demonstrated the efficacy of antacids and surface coating preparations in controlling GERD symptoms. The widespread use of these drugs testifies to an efficacy that nevertheless remains limited to mild forms of GERD (intermittent forms without severe esophagitis lesions) and to forms having responded well initially. These medications have no curative action nor do they prevent esophagitis. Because of potential drug interactions with other medications, antacids should be taken separately.4.3. H2 blockers
Initial H2 antagonist therapy often leads to a significant reduction in esophagitis symptoms and lesions. However, when compared to placebo, the symptomatic improvement is usually under 20% and the healing rate is about 50%. The results are generally disappointing in cases of severe esophagitis lesions or complicated forms of the disease. H2 blockers are best suited for the symptomatic treatment of uncomplicated GERD and mild forms of esophagitis. Because of a lower incidence of drug interaction with ranitidine, famotidine and nizatidine, these are generally preferred over cimetidine. The daily dose is the same as that used for duodenal ulcer treatment and should be divided into twice daily dosage. A 4 to 6-week treatment is indicated.The efficacy of low dose H2 blockers compared to placebo in the symptomatic treatment of reflux has been documented. The fast action forms of H2 blockers (effervescent tablets, sublingual and chewable forms) seem well adapted for immediate relief of GERD symptoms.
Despite their safety of administration, the role of H2 blockers in the treatment of GERD has been considerably reduced, in light of the efficacy of gastric PPIs. However, new treatment modalities (self-medication, treatment on request) which have been developed over the past few years seem to be of interest and deserve further evaluation.
4.4. Gastric proton pump inhibitors (PPIs)
The efficacy of PPIs on symptomatic relief and healing of esophagitis lesions, no matter how severe, is superior to that of all other therapeutic classes ( Johanson et al ., 2002 ).A meta-analysis of the major trials that have been published reports an 84% healing rate of esophageal lesions after 4 to 8 weeks of treatment – which is far superior to the rate obtained with H2 blockers (58%) or placebo (28%). Similar figures were obtained concerning the disappearance of symptoms. These results are also observed during maintenance treatments. This superiority is particularly significant in severe forms of esophagitis. No clinically significant difference has been demonstrated between currently available PPIs at standard doses.
For peptic stricture, PPIs are the only therapeutic class proven to be effective on symptoms, healing of mucosal injuries, and frequency of endoscopic dilatations. They are not effective on Barrett’s esophagus, however, and in this context, their usefulness in combination with endoscopic ablation techniques of the metaplastic or dysplastic mucosa is currently under evaluation.
Further studies are indicated to evaluate the efficacy of different treatment regimens for atypical forms of GERD. In the meantime, a single or double dose PPI treatment over a 4 to 8-week period is proposed when the diagnosis of GERD is strongly suspected or confirmed.
Recent studies have explored the possibilities of reducing or spacing out PPI doses. The symptomatic efficacy of half doses has been demonstrated on moderate forms of GERD (without esophagitis or with mild esophagitis), for both short-term intensive therapy and maintenance therapy. Preliminary data suggest that the efficacy of lanzoprazole at half dose and at standard dose is identical. On the other hand, increasing the dosing interval of drug intake (alternating treatment every other day or 3 days a week) cannot be recommended.
Overall, PPIs are well tolerated and cause no significant side effects.
4.5. Consequences of achlorhydria and Helicobacter pylori infection
Prolonged antisecretory therapy can result in intestinal bacterial overgrowth, infectious diarrhea or vitamin B12 malabsorption. These side effects are often clinically minor and should not be a deterrent when planning antisecretory therapy or surveillance.Prolonged significant antisecretory therapy can induce hypergastrinemia as well as Enterochromaffin-like cellular hyperplasia in the gastric fundus. At the present time, with a 10-year follow-up, these effects do not seem to be of clinical significance. Routine monitoring of gastrin levels or gastric histology is therefore not indicated in patients treated with long-term PPIs.
The role played by Helicobacter pylori in the pathophysiology of GERD or atrophic gastritis is not clearly established. On the other hand, eradication of Helicobacter pylori could diminish the efficacy of PPI therapy. Currently, there is not enough evidence to support systemic detection and treatment of Helicobacter pylori infection in cases of prolonged PPI therapy. There is not enough proof to justify a systematic search for this bacterium and its elimination during long-term antisecretory treatment.
1. Introduction
2. Diagnosing GERD
3. Assessing GERD
4. Medical therapy
5. Therapeutic strategy
6. Surgical therapy
7. References
5.
Therapeutic strategy
5.1. Self-medication
Nearly two thirds of patients suffering from heartburn do not seek medical attention and many of them treat themselves with over-the-counter medications. This therapeutic option, based on topical agents and fast acting, low-dose H2 blockers, seems to be effective in reducing symptoms, although its clinical efficacy needs to be established by further studies. The risks of self-medication (side effects, drug interactions and delayed diagnosis of neoplasia) seem to be very low considering their current use.We do not condemn or condone this self-medication approach. The drug information delivered along with the medication should be as informative and educational as possible, with special attention devoted to the symptoms necessitating medical attention. The creation and validation of these information sheets should be the result of a team effort including doctors, pharmacists and consumer representatives.
5.2. Initial strategy
Up to now, no study has clearly, completely, and accurately evaluated the ideal way to initiate therapy in patients with GERD. An ascendant therapeutic approach would progress from the least active to the most active therapy as opposed to a descendant approach. Both strategies aim at defining the minimal effective therapy – yet neither is ideal since they may over- or underestimate therapeutic needs. Based on the current state of scientific and medical-economic information available, the following treatment strategies are the most appropriate with regard to the variability in clinical presentation and efficacy of GERD therapy ( Ofman, 2002 ):a. In cases of occasional typical reflux symptoms and in the absence of alarming symptoms: antacids, alginic acid or low-dose H2 blocker treatment as needed. These 3 drug classes have equivalent symptomatic efficacy. Postural and dietary measures should be added to this.
b. In case of typical repeated reflux symptoms (at least once a week) in the absence of alarming signs in patients < 50 years old: 4-week course of therapy with half-dose PPIs or full-dose H2 blockers or cisapride (if no contraindication). In case of successful results, the treatment must be stopped at the end of the 4-week period. If the treatment is ineffective or the symptoms recur early, an upper gastrointestinal endoscopy is recommended.
c. Endoscopy is also recommended in patients > 50 years old or suffering from alarming symptoms. In cases of non-severe or absent esophagitis, a 4-week course of therapy with antisecretory medications (PPIs are best) must be considered. If the reason for the endoscopy is therapeutic failure, then full-dose treatment with PPIs must be administered. In cases of severe esophagitis or peptic complications, a full-dose 8-week course of PPIs must be administered and monitored by endoscopy. If healing has not occurred or if symptoms persist, dosage increase must be considered.
d. When extra-intestinal symptoms appear, a standard or double-dose 4 to 8-week PPI treatment should be administered, on the condition that the diagnosis of reflux is well established or very strongly suspected.
5.3. Long-term strategy in the absence of complications
a. The initial treatment should be stopped when the symptoms disappear, except in cases of severe esophagitis or complications.b. In the frequent cases of relapsing symptoms (with or without mild esophagitis), the patient can be treated in an intermittent fashion using a similar regimen to the one that allowed initial recovery.
Frequent or premature recurrences after the end of the therapy have a significant impact on the patient’s quality of life (QOL) and in these cases, maintenance therapy with individualized dosage of PPIs is indicated. Endoscopic surveillance after the therapy is not indicated if the symptoms are well controlled. Initial therapy should not be interrupted in patients with severe esophagitis.
When maintenance therapy is required, the decision to continue medical treatment or to resort to surgical therapy must involve the patient.
5.4. Treating complications
Peptic strictureTreatment of peptic stricture requires standard-dose PPI therapy. In cases of dysphagia, endoscopic dilatation is used in association with medical therapy. In the absence of esophageal healing, the PPI dosage must be increased. Treatment should be pursued continuously at the effective dosage. In 30% to 50% of cases, repeated endoscopic dilatations after a 1-year follow-up are necessary despite continuous PPI therapy. The choice between the use of bougie versus pneumatic dilatation is currently controversial due to contradictory study results. Further studies are therefore needed to better define the superiority of one modality over the other.
Surgical therapy must be considered in cases of failure of medical therapy. In the remainder of cases, the choice between prolonged medical therapy and surgery must be discussed using the same criteria as presented above for uncomplicated GERD.
Barrett’s esophagus
Medical therapy with PPI is effective for symptom control as well as for curing esophagitis. High doses may be required. Asymptomatic cases do not require therapy.
Long-term antisecretory therapy or surgical therapy have not been proven to lead to a complete regression of Barrett’s esophagus or to prevent progression to dysplasia and carcinoma. Continued endoscopic and histologic surveillance is therefore mandatory, even after surgery for GERD ( Csendes et al ., 2002 ).
The use of thermal or photochemical ablation techniques must be conducted in the setting of clinical trials in specialized centers. They are indicated for patients who have a very high risk of malignant transformation (dysplasia). Early results show they allow squamous re-epithelialization of the distal esophagus but their efficacy in reducing the risk of carcinoma remains to be demonstrated.
1. Introduction
2. Diagnosing GERD
3. Assessing GERD
4. Medical therapy
5. Therapeutic strategy
6. Surgical therapy
7. References
6.
Surgical therapy
The goal of surgical therapy is to recreate an anti-reflux barrier. It is the only treatment capable of changing the natural history of GERD. There has been renewed interest in this therapy with the advent of laparoscopic surgery. The principles of surgical therapy remain unchanged, however: reduction of hiatal hernias and recreation of an anti-reflux mechanism on the distal esophagus using the fundus of the stomach.6.1. Preoperative evaluation
There are 2 goals in preoperative assessment: confirming the pathological aspect of the reflux and ruling out any surgical contraindications. Due to the lack of sufficient evidence and frequent disagreements among experts (as seen in the multitude of conflicting conclusions of consensus conferences and good clinical practice guides), there are no universal recommendations. The following recommendations are proposed:-
Upper gastrointestinal endoscopy (EGD): required for diagnostic purposes.
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pH monitoring: essential in the absence of esophageal lesions.
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Esophageal manometry: generally recommended during preoperative examination for the following reasons:
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to avoid missing intrinsic esophageal motor abnormalities contraindicating a surgical intervention (achalasia, scleroderma);
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to serve as reference data for postoperative follow-up;
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to identify associated severe motor dysfunction of the esophagus, even if the practical consequences of such findings are controversial.
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to avoid missing intrinsic esophageal motor abnormalities contraindicating a surgical intervention (achalasia, scleroderma);
Esophageal manometry
Performance of the exam:
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The patient has been fasting for at least 6 hours.
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He is placed in right lateral supine position.
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No pre-medication other than nasal topical anesthesia.
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Many medications affect esophageal motility and should be discontinued at least 12 hours before the examination
Table 6.1: Medication that may interfere with esophageal manometry results
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Esophageal manometry
The manometric exam evaluates:
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the lower esophageal sphincter (LES);
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the body of the esophagus;
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the upper esophageal sphincter (UES).
The value of manometry is nevertheless limited because:
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it does not identify patients who will develop postoperative dysphagia,
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it does not modify the operative strategy (full or partial wrap).
6.2. Surgical technique and results
The evidence currently available attests to the superiority of fundoplication, making it the procedure of choice for the treatment of GERD. There is no sufficient evidence, however, to demonstrate the superiority of either total or partial fundoplication. The good long-term efficacy of total fundoplications, as published in some series, must be weighed against the lower morbidity of partial fundoplications.Despite weak scientific evidence and lack of long-term follow-up, laparoscopy can be considered the preferred modality for the treatment of uncomplicated GERD. Several prospective randomized trials have compared laparotomy to laparoscopy; they show less abdominal wall (parietal) morbidity and a shorter hospitalization for the laparoscopic treatment with overall similar functional results.
6.3. What are the indications for surgical treatment?
SAGES guidelines ( http://www.sages.org/sg_pub22.html , revised in June 2001)Surgical therapy should be considered in individuals with documented GERD who:
a. are not compliant to medical therapy,
or
b. opt for surgery despite successful medical management (due to lifestyle considerations including age, time, or expense of medications),
or
c. have complications of GERD (eg, Barrett’s esophagus, stricture, grade 3 or 4 esophagitis),
or
d. have “atypical” symptoms (asthma, hoarseness, cough, chest pain, aspiration) and reflux documented on 24-hour pH monitoring.
Consensus conference of the European Association for Endoscopic Surgery (1997 ).
Even after successful medical acid suppression, the patient can have recurrent symptoms of epigastric pain and retrosternal pressure as well as food regurgitation due to an incompetent cardia, insufficient peristalsis, or a large hiatal hernia.
Concerning the indication for surgery, a distinction between heartburn and regurgitation symptoms is considered important (medical treatment appears to be more effective for heartburn than for regurgitation). Therefore the indication for surgery is based on the following facts:
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non-compliance of the patient with ongoing effective medical treatment. Reasons for non-compliance are preference, refusal, reduced quality of life, drug dependency and drug side effects,
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persistent or recurrent esophagitis in spite of currently optimal medical treatment and with or without symptoms,
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persistent regurgitation;
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complications of the disease: ulcers, stenoses, and Barrett’s esophagus have minor influence on the indication (neither medical nor surgical treatment has been shown to alter the extent of Barrett’s epithelium).
NOTE: Patients with symptoms completely resistant to antisecretory treatment with PPIs are bad candidates for surgery. In these individuals other diseases have to be investigated carefully.
Good candidates for surgery should have a positive response to antisecretory drugs.
AUTHOR’S NOTE:
Item “c” from the SAGES Guidelines and the last item from the EAES Guidelines seem to be in conflict, which underlines the ongoing debate on indications for surgery in the treatment of GERD.
1. Introduction
2. Diagnosing GERD
3. Assessing GERD
4. Medical therapy
5. Therapeutic strategy
6. Surgical therapy
7. References
7.
References
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Laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD). Results of a Consensus Development Conference. Held at the Fourth International Congress of the European Association for Endoscopic Surgery (E.A.E.S.), Trondheim, Norway, June 21-24, 1996. Surg Endosc 1997;11:413-26.
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Csendes A, Burdiles P, Braghetto I, Smok G, Castro C, Korn O
et al.
Dysplasia and adenocarcinoma after classic antireflux surgery in patients with Barrett's esophagus: the need for long-term subjective and objective follow-up. Ann Surg 2002;235:178-85.
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Falk GW. Barrett's esophagus. Gastroenterology 2002;122:1569-91.
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Incarbone R, Bonavina L, Bassi F, Peracchia A. [Impact of endoscopic surveillance of Barrett's esophagus on survival of patients with esophageal adenocarcinoma]. Chir Ital 2002;54:591-6.
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Johanson JF, Siddique R, Damiano AM, Jokubaitis L, Murthy A, Bhattacharjya A. Rabeprazole improves health-related quality of life in patients with erosive gastroesophageal reflux disease. Dig Dis Sci 2002;47:2574-8.
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Ofman JJ. Decision making in gastroesophageal reflux disease. What are the critical issues? Gastroenterol Clin North Am 2002;31:S67-76.
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Shaheen N, Ransohoff DF. Gastroesophageal reflux, barrett esophagus, and esophageal cancer: scientific review. Jama 2002;287:1972-81.
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Spechler SJ. Barrett's esophagus and esophageal adenocarcinoma: pathogenesis, diagnosis, and therapy. Med Clin North Am 2002;86:1423-45, vii.