Updated Guidelines for the Diagnosis and Treatment ofGastroesophageal Reflux DiseaseKenneth R. DeVault M.D., F.A.C.G., and Donald O. Castell M.D., M.A.C.G.
Departments of Medicine, Mayo Clinic College of Medicine, Jacksonville, Florida; and Medical University ofSouth Carolina, Charleston, South Carolina Guidelines for the diagnosis and treatment of gastroesophageal reflux disease (GERD) werepublished in 1995 and updated in 1999. These and other guidelines undergo periodic review.
Advances continue to be made in the area of GERD, leading us to review and revise previousguideline statements. GERD is defined as symptoms or mucosal damage produced by the abnormalreflux of gastric contents into the esophagus. These guidelines were developed under the auspicesof the American College of Gastroenterology and its Practice Parameters Committee, and approvedby the Board of Trustees. Diagnostic guidelines address empiric therapy and the use of endoscopy,ambulatory reflux monitoring, and esophageal manometry in GERD. Treatment guidelines addressthe role of lifestyle changes, patient directed (OTC) therapy, acid suppression, promotility therapy,maintenance therapy, antireflux surgery, and endoscopic therapy in GERD. Finally, there is adiscussion of the rare patient with refractory GERD and a list of areas in need of additional study.
sented. When scientific data were lacking, recommendationswere based on expert consensus obtained from both the lit- Guidelines for the diagnosis and treatment of gastroe- erature and the experience of the authors and the Practice sophageal reflux disease (GERD) were published by the Parameters Committee. The committee evaluated each ital- American College of Gastroenterology in 1995 and updated icized guideline and a strength of evidence score was given in 1999 (1, 2). These and other guidelines undergo periodic review. Advances continue to be made in the area of GERD,leading us to review and revise our previous guidelines state-ments. These and the original guidelines are intended to ap- DIAGNOSTIC GUIDELINE I: EMPIRICAL THERAPY
ply to all health-care providers who address GERD and areintended to indicate the preferred, but not only, acceptable ap- If the patient’s history is typical for uncomplicated GERD, an proach. Treatment should be based on the course best suited initial trial of empirical therapy (including lifestyle modifi- to the individual patients and the variables that exist at the mo- cation) is appropriate. Endoscopy at presentation should be ment of the decision. These guidelines are applicable to adult considered in patients who have symptoms suggesting com- patients with the symptoms, tissue damage, or both that result plicated disease, those at risk for Barrett’s esophagus, or from the reflux of gastric content into the esophagus. For the when the patient and physician feel early endoscopy to be purpose of these guidelines, GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastriccontents into the esophagus. Level of Evidence: IV
These and the previous guidelines were developed under Symptoms which are highly specific for GERD include heart- the auspices of the American College of Gastroenterology burn (pyrosis), regurgitation, or both, which often occur after and its Practice Parameters Committee, and approved by the meals (especially large or fatty meals) (3). These symptoms Board of Trustees. The world literature was reviewed exten- are often aggravated by recumbency or bending over and are sively for the original guidelines and again reviewed for each relieved by antacids. The combination of symptoms and en- revision using the National Library of Medicine database.
doscopic changes are highly specific (97%) for GERD (con- Appropriate studies were reviewed and any additional stud- firmed with pH testing) (4). Expert opinion holds that it is ies found in the reference list of these papers were obtained appropriate to offer empirical therapy for GERD to patients and reviewed. Evidence was evaluated along a hierarchy, with with symptoms consistent with GERD. It is also reasonable randomized, controlled trials given the greatest weight. Ab- to assume a diagnosis of GERD in patients who respond to stracts presented at national and international meetings were appropriate therapy. Further diagnostic testing should be con- only used when unique data from ongoing trials were pre- sidered if the patient does not respond to therapy, when there Updated Guidelines for Diagnosis and Treatment of GERD
Table 1. Rating of Levels of Evidence Used for this Guideline
rett’s esophagus. A reticular pattern on barium esophagram is I Strong evidence from at least one published systematic neither sensitive (26%) nor specific (50%) when compared to review of multiple well-designed randomized controlled endoscopy with biopsy (11). Barium radiography is reason- ably accurate in cases of severe esophagitis (80% or better), II Strong evidence from at least one published properly but is much less accurate with mild esophagitis (less than designed randomized controlled trial of appropriate size 25%) (12–15). Finally, reflux of barium during radiographic III Evidence from published well-designed trials without evaluation is only positive in 25–75% of symptomatic pa- randomization, single group prepost, cohort, time series tients and is falsely positive in up to 20% of normal controls (15, 16). Patients with hiatal hernias or who reflux barium at IV Evidence from well-designed nonexperimental studies from fluoroscopy have more acid exposure by ambulatory pH test- more than one center or research group or opinion of ing, but these findings have poor specificity and sensitivity respected authorities, based on clinical evidence,descriptive studies, or reports of expert consensus and should not be used as a screening test for GERD (17).
These factors limit the usefulness of barium radiography inthe routine diagnosis of GERD and it is not recommended.
Documentation of the presence or absence of esophagitis does not usually determine the initial approach to patients are alarm symptoms suggesting complicated disease (dys- with GERD. Higher grades of esophagitis are more difficult phagia, odynophagia, bleeding, weight loss, or anemia) and to heal, but once healed can be maintained in remission with when patients have a sufficient duration of symptoms to put medical or surgical therapy (18, 19). The main advantage of them at risk for Barrett’s esophagus. Patients who do not re- knowing a patient has (or had) esophagitis is to confirm the spond to therapy often have another cause for their symptoms, diagnosis of GERD prior to surgical or endoscopic therapy but this lack of response does not always exclude reflux as a for GERD. Typical esophagitis is essentially diagnostic for possibility. Even when the most effective therapy for GERD is prescribed, some patients will continue to reflux acid (5).
Endoscopic biopsy is needed to determine the presence A short trial of a high dose proton pump inhibitor has 75% of Barrett’s epithelium. The issues surrounding the manage- sensitivity, but only 55% specificity for reflux in heartburn pa- ment of Barrett’s are covered in another guideline statement tients using ambulatory pH testing as the “gold standard” (6).
(20). Although not proven, this endoscopy probably should These problems with the sensitivity and specificity of using a be performed after a course of therapy for GERD to allow bet- therapeutic trial as a test for GERD must be weighed against ter identification of Barrett’s and to decrease the prevalence the ease of use and decreased cost (primarily related to de- of inflammatory changes that are misinterpreted as dyspla- creased use of diagnostic testing of this approach) (7). Finally, sia. It is of paramount importance that the esophagogastric symptoms do not seem to predict the degree of esophagitis junction is well described in the endoscopy report. Biopsies and are far from perfect in predicting complications of GERD showing intestinal metaplasia, identical to Barrett’s, which including Barrett’s esophagus (8).
are obtained from the gastric cardia do not indicate the same The purpose of evaluating patients with long-term symp- malignant potential as biopsies from the esophagus and ac- toms and patients who have complicated symptoms is to ex- tually do not even confirm GERD (21). There is no value for clude complications of GERD. Compared with patients with histologic examination of normal appearing squamous mu- symptoms consistent with GERD for less than 1 yr, the odds cosa to either confirm or exclude pathologic acid reflux (22, ratio for Barrett’s esophagus in patients with symptoms for 1–5 yr is 3.0 and for greater than 10 yr is 6.4. These concepts It is critical to understand that while an endoscopy show- have been challenged by reports suggesting that both the fre- ing clear evidence of Barrett’s esophagus or esophagitis con- quency and severity of reflux symptoms are poorly predictive firms the diagnosis of GERD, a normal endoscopy in no of the presence of Barrett’s esophagus (9, 10). Patients with way excludes GERD. The majority of symptomatic patients alarm symptoms are more likely to have peptic strictures and will have a normal endoscopy, which does not necessar- esophagitis than those without alarm symptoms.
ily indicate either less severe symptoms or a more easy tocontrol form of GERD (24). In fact, studies of GERD pa-tients without esophagitis have suggested that symptoms DIAGNOSTIC GUIDELINE II: USE OF ENDOSCOPY IN GERD
are just as difficult and at times more difficult to control Endoscopy is the technique of choice used to identify sus- (25). The suggestion that only patients with documentable pected Barrett’s esophagus and to diagnose complications esophagitis should have access to chronic proton pump in- of GERD. Biopsy must be added to confirm the presence of hibitor therapy is not supportable, since these patients may Barrett’s epithelium and to evaluate for dysplasia. well have pathologic amounts of acid reflux that is onlycontrolled with a PPI (26). Symptomatic GERD patients Level of Evidence: III
without esophagitis (so called nonerosive reflux disease) Endoscopy allows direct visualization of the esophageal mu- should be treated in a similar fashion to those with erosive cosa. This is the only reliable method for the diagnosis of Bar- DeVault and Castell
Esophageal manometry may be used to ensure accurate Ambulatory monitoring of the esophagus helps to confirm placement of ambulatory monitoring probes and may be help- gastroesophageal reflux in patients with persistent symptoms (both typical and atypical) without evidence of mucosal dam-age, especially when a trial of acid suppression has failed. It Level of Evidence: III
may also be used to monitor the control of reflux in patients The accurate placement of esophageal pH probes requires with continued symptoms on therapy. knowledge of the location of the lower esophageal sphincter(39, 40). This usually requires intubation with a manome-try catheter and provides an opportunity for full manome- Level of Evidence: III
try. There now have been several reports that show adequate While endoscopy allows for the evaluation of esophageal mu- placement of pH tubes using a combined pH/pressure mea- cosa, the presence or absence of mucosal injury does not pro- surement system, which negates the need for full manometry vide proof that the patient’s symptoms are or are not related (41, 42). The new tubeless pH monitoring system uses en- to GERD. Many patients with typical GERD symptoms and doscopic landmarks for placement, which were derived from increased esophageal acid exposure do not have esophagitis studies comparing endoscopic to manometric measurements (27). Patients with symptomatic, but not excessive gastroe- sophageal reflux have persistence of symptoms and require- Esophageal manometry to document the presence of ef- ments for therapy similar to patients with excessive reflux, fective esophageal peristalsis has been used in patients in but are less likely to have endoscopic findings (28). This “en- whom antireflux surgery is being considered (43). It has doscopic negative” form of GERD produces symptoms and been suggested that patients who have ineffective peristalsis illness behavior identical to that of GERD with endoscopic may need to either avoid surgery or undergo an alternative findings (29). Ambulatory pH testing allows both the iden- (i.e., less tight) procedure (44). Surgeons will often elect tification of patients with excess esophageal acid exposure to perform a partial fundoplication in patients who have a and those with symptoms that correlate with esophageal acid weaker esophagus by manometry (45). In a series of 107 (either with normal or abnormal total acid exposure). Good patients, manometry changed the therapy offered in 10% of reproducibility (84–93%) and sensitivity and specificity patients referred for antireflux surgery (46). These assump- (96%) have been reported in patients with erosive esophagitis tions have recently been challenged by several studies. For (30, 31). Reasons for concern include the finding of normal example, reflux control was found to be better and dyspha- acid exposure in up to 29% of patients with documented gia no more common in several series of patients with weak esophagitis and differences found in the simultaneous acid peristalsis when a complete, as opposed to a partial, fundopli- exposure recorded by two attached probes (32, 33). A recent cation was performed (47, 48). A recent report of combined report repeated pH testing on patients who had an initial neg- impedance and manometry testing suggests that this tech- ative test (34). If the patient’s symptoms had been typical or nique may have the ability to identify which patients with worse than typical during their first pH test, 22% of second ineffective peristalsis have an esophageal bolus transit abnor- tests were positive, while 55% of studies were abnormal if mality, therefore potentially clarifying which patients have a the patients said their day was “better than typical” during more significant defect in motility (49). Preoperative manom- the first test. Despite these limitations, ambulatory pH test- etry is perhaps most useful to exclude rare motility disorders ing remains the best method to study the actual amount of such as achalasia or the aperistalsis associated with disorders reflux occurring in a given patient. Ambulatory pH testing while on reflux therapy may also be of benefit in the patientwith refractory symptoms (35).
There have been two recent advances that may alter the TREATMENT GUIDELINE I: LIFESTYLE MODIFICATION
management of GERD. Combined impedance and acid test-ing has been developed (36, 37). This technology allows for Lifestyle modification may benefit many patients with GERD, the measurement of both acid and nonacid (volume) reflux.
although these changes alone are unlikely to control symp- This may be particularly important in the patient with persis- tent symptoms despite an adequate medical trial and allowmore efficient monitoring of reflux in patients on therapy.
Level of Evidence: IV
Another new technology is a tubeless method of acid mon- Education of the patient about factors that may precipitate itoring. This device allows a radiotelemetry capsule to be reflux remains reasonable. Numerous studies have indicated attached to the esophageal mucosa and monitored without that elevation of the head of the bed (50, 51), decreased fat the discomfort of a nasoesophageal tube (38). This decreases intake (52), cessation of smoking (53), and avoiding recum- patient discomfort, allows for longer (48 h) monitoring, and bency for 3 h postprandially (54) decreases distal esophageal may improve accuracy by allowing the patient to carry out acid exposure although data reflecting the true efficacy of these maneuvers in patients is almost completely lacking.
Updated Guidelines for Diagnosis and Treatment of GERD
Certain foods (chocolate (55), alcohol (56), peppermint (57), and differences in FDA indications, dosages, and adminis- coffee (58), and perhaps onions and garlic (59)) have been noted to lower LES pressure, although randomized trials arealso not available to test the efficacy of these maneuvers.
Many authors assume the 20–30% placebo response rate seen TREATMENT GUIDELINE III: ACID SUPPRESSION
in most randomized trials is due to lifestyle changes, but thishas not been rigorously tested. The potential negative effect Acid suppression is the mainstay of therapy for GERD. Pro- of lifestyle changes on a patient’s quality of life has also not ton pump inhibitors provide the most rapid symptomatic relief and heal esophagitis in the highest percentage of patients. Al-though less effective than PPIs, histamine2-receptor blockersgiven in divided doses may be effective in some patients withless severe GERD. TREATMENT GUIDELINE II: PATIENT DIRECTED THERAPY
Antacids and over-the-counter (OTC) acid suppressants are Level of Evidence: I
options for patient-directed therapy for heartburn and re- In the original guideline statement (1), the results of 33 ran- gurgitation. When symptoms persist, continuous therapy is domized trials including over 3,000 patients with erosive required or alarm symptoms or signs develop, the patient esophagitis are presented. Symptomatic relief can be ex- should have additional evaluation and treatment (see above pected in 27% of placebo treated, 60% of H2RA treated, and 83% of PPI treated patients. Esophagitis healed in 24%of placebo treated, 50% of H2RA treated, and 78% of PPI Level of Evidence: IV
treated patients. We will not readdress those studies here, Antacids and antirefluxants such as alginic acid are useful in but it is clear that while some patients may have relief of the treatment of milder forms of GERD. Antacids (60) and symptoms and improvement or healing of esophagitis on alginic acid (61, 62) have been shown to be more effective H2RAs, PPIs eliminate symptoms and heal esophagitis more than placebo in the relief of symptoms induced by a heartburn frequently and more rapidly than the other agents. Both higher promoting meal. In addition, combined antacid/alginic acid doses and more frequent dosing of H2RAs appear to improve therapy may be superior to antacids alone in the control of results in the treatment of reflux, but are still inferior to PPIs symptoms (63, 64). There are two long-term trials, which (67–69). In addition to controlling symptoms and esophagi- suggest effective symptom relief in approximately 20% of tis, PPI therapy has been shown to normalize the impaired quality of life caused by GERD (70).
All four of the H2RAs approved for use in the United States Proton pump inhibitors are safe, effective, and have been are available OTC in doses that have been shown to decrease used for more than a decade in the United States and much gastric acid, particularly after a meal. While there are some longer in Europe and Australia (71). It is becoming increas- differences in potency, duration, and rapidity of action, they ingly clear that the benefit of chronic PPI therapy in patients may be generally used interchangeably. The OTC H2RAs are with chronic and/or complicated GERD outweighs any the- particularly useful when taken prior to an activity that may oretical risk. Some concerns have been raised about the pos- potentially result in reflux symptoms (heavy meal or exercise sibility of vitamin B-12 deficiency occurring on chronic PPI in some patients). Many patients can predict when they are therapy, although this has only been reported in a few patients going to suffer from reflux and can premedicate with the OTC H2RAs. Comparisons between OTC H2RAs and antacids are There are five available PPIs (omeprazole, lansoprazole, limited. It has been suggested that antacids provide a more rabeprazole, pantoprazole, and esomeprazole). All of these rapid response, but gastric pH begins to rise less than 30 min agents have been demonstrated to control GERD symptoms after taking a dose of H2RA so this does not seem to be a and to heal esophagitis when used at prescription dosages.
major factor. The peak potency of OTC H2RAs and antacids There have been several physiologic studies suggesting mod- are similar, but the H2RAs have a much longer duration of est benefits of one agent over another (73–77). The effect action (up to 10 h). An OTC formulation of omeprazole has of PPIs can be optimized with appropriate dosing. The drugs just been introduced in the United States at a dose identical should always be given prior to meals. Most patients on once- to that available by prescription for the short-term (14 days) daily PPI should take them prior to breakfast, but a recent treatment of heartburn. It is important that patients visit their study suggested that nighttime acid might be better controlled physician before using these medications beyond their 14-day if the PPI is taken prior to the evening meal (78). In some sit- indication since some will be at risk for Barrett’s esophagus uations, it is reasonable to use higher than approved doses of or other upper gastrointestinal pathology and should be eval- PPI, which are then often given in divided doses. Times when uated and, if appropriate, referred for endoscopic screening.
this is of particular benefit are during a diagnostic trial for It is important that physicians and their patients continue to noncardiac chest pain (79), during empiric treatment trial for have access to prescription proton pump inhibitors (PPIs) for supraesophageal symptoms of GERD (80), in patients with a several reasons including difference in individual response partial response to standard dose therapy (5), in patients who DeVault and Castell
have responded but are having breakthrough symptoms (71), tral to the pathogenesis of GERD (89). If these defects could in GERD patients with severe esophageal dysmotility (81), be corrected then GERD would be controlled, making sup- and in patients with Barrett’s esophagus (82). When a second pression of normal amounts of gastric acid unnecessary. The dose is added, it should be given prior to the evening meal, frequent Central Nervous System side effects of metoclo- pramide and bethanechol (drowsiness, irritability, extrapyra- It is clear that PPI therapy results in the best symptom midal effects, etc.) have appropriately decreased the regular control and esophagitis healing among our available medi- use of these medications (90). Cisapride (91, 92) and dom- cal options. It is also clear that some patients (although it peridone (93) have been demonstrated to produce relief of is difficult to determine which patients) will do well on the symptoms. There have been reports of fatal cardiac dysrhyth- less intense acid suppression resulting from H2RA therapy.
mias associated with the combination of cisapride and several Several strategies have been advocated to decrease the cost agents that are metabolized by the cytochrome P-450 system of GERD therapy by limiting the number of patients taking (94). These reactions and a more recent suggestion of mecha- PPI. These strategies have been examined in many model- nisms for the production of similar rhythm disturbances while ing analyses, but have not been well tested in randomized on cisapride alone have resulted in the withdrawal of this trials. A recent study in a VA population demonstrated that agent from regular availability in the United States market patients who were “PPI dependent” could frequently be man- (95). Domperidone is a dopamine receptor blocker but un- aged on less intense therapy (83). They attempted to take 71 like metoclopramide does not easily cross the blood-brain patients off PPIs finding that 42% could not be taken off, 42% barrier and therefore has little central nervous system effect.
could be managed with H2RAs, prokinetics, or a combina- Domperidone is as effective as metoclopramide and the only tion, and 15% could be taken off medication. It is unclear if significant side effect seems to be hyperprolactinemia in 10– these data can be applied to a more generalized population.
15% of patients. Despite this safety profile, the agent has not Modeling studies that use cost as an important endpoint are been marketed in the United States. Tegaserod is a 5HT3 ag- highly dependent on the assumptions used in constructing onist with promotility and antinociceptive affects. It has been the model. Efficacy and safety data support continuous PPI shown to improve esophageal acid exposure (96), but has not therapy as the most effective management for patients with been demonstrated to be effective monotherapy in GERD.
GERD. The only advantage for using less effective therapy Finally, baclofen, a GABA receptor type B agonist, has been is economic and the current availability of both generic and reported to reduce both the number of reflux episodes and OTC PPIs makes continuous PPI therapy even more attrac- percent time esophageal acid exposure after a single dose of tive. On-demand therapy with PPIs has not been well studied, 40 mg (97). The mechanism appears to be suppression of tran- but patients tend to do this on their own and it may make sient LES relaxation (98). This agent has a high side-effect economic sense in patients with mild-to-moderate symptoms profile and probably will not be routinely used in patients, (84). Once a patient has failed less effective therapy, they but there is intensive research ongoing to find a baclofen-like should have access to chronic PPI therapy, especially if it is agent with a better side-effect profile. In summary, continued the only medical therapy that keeps them in symptomatic and research into the role of promotility agents in GERD is war- ranted, but acid suppression remains the mainstay of GERD The benefit of complete acid control in the maintenance of Barrett’s esophagus has not been proven, but if this result isdesired, many patients will need twice daily PPI therapy athigher than usual doses even when the patients are asymp- TREATMENT GUIDELINE V: MAINTENANCE THERAPY
tomatic on lower doses (85, 86). Gastric acid is still secreted,particularly at night, in many patients on twice-daily PPIs Because GERD is a chronic condition, continuous therapy to (87). The addition of a nighttime H2RA was suggested to control symptoms and prevent complications is appropriate. suppress this acid, although a recent study found that thiseffect might not persist over time (88).
Level of Evidence: I
The improvement in GERD symptoms noted with the acid
suppression produced by full dose PPIs is usually followed
by a rapid return of symptoms once it is discontinued (99).
Many patients with GERD require long-term, possibly life- Promotility agents may be used in selected patients, espe- long, therapy; therefore maintenance therapy becomes a ma- cially as an adjunct to acid suppression. Currently available jor concern. Effective maintenance therapy should keep the promotility agents are not ideal monotherapy for most pa- patient’s symptoms comfortably under control and prevent complications. This will vary in each patient and may requireonly antacids and lifestyle modifications in up to 20% of pa- Level of Evidence: II
tients (84). Other patients with chronic reflux (up to 50%) Defects in esophagogastric motility (LES incompetence, poor have frequent symptomatic relapses despite appropriate ther- esophageal clearance, and delayed gastric emptying) are cen- apy. Patients whose disease has been controlled with PPIs Updated Guidelines for Diagnosis and Treatment of GERD
often will have symptomatic relapses and failure of healing pletely resolved on medical therapy (114). It is also clear that of esophagitis on standard dose, or even higher-dose H2RA these typical reflux symptoms are more likely to resolve after and/or prokinetic therapy (100). A full dose of H2RA given surgery than the other atypical and supraesophageal symp- once daily, although effective for peptic ulcer disease, is not appropriate for GERD. Reduced doses of PPIs have been If typical reflux esophagitis is not present endoscopically, consistently shown to be ineffective long-term in the therapy ambulatory pH testing should be performed. Controversies of GERD. This includes alternate day omeprazole (101) or related to the use of manometry to guide antireflux surgery “weekend” therapy (102). A daily dose of omeprazole 10 mg are discussed in the above section on manometry. Delayed may be superior to standard dose ranitidine (103). Ultimately, gastric emptying has been reported to increase the rate of whatever dose of medication is needed to control symptoms complication following an antireflux surgery, but the utility is the dose that should be used and may include full or even of the routine preoperative use of these tests is not clear (116).
increased dose PPI in many patients.
The medical therapy of GERD has focused on the neu- There are clear data that acid suppression decreases tralization of refluxed acid from the stomach. It is clear that the recurrence of peptic esophageal strictures. Cimetidine there are other injurious factors involved. The possibility of 400 mg four times a day did not affect the frequency of the duodenogastroesophageal reflux has been raised as an addi- need for dilation (104), but several studies have found that full tional indication for the surgical repair of the LES in patients dose PPIs will lengthen the interval between symptomatic re- with GERD (117). While it appears that control of acid de- lapses (105, 106). There are no similar data in regards to the creases the injury in patients who reflux duodenal contents prevention or prevention of progression of Barrett’s esopha- (118, 119), certain of these patients may benefit from antire- gus. It does not appear that Barrett’s esophagus will regress flux surgery although objective evidence of this type of reflux with either medical or surgical therapy (107, 108). There have is difficult to obtain preoperatively.
been reports of occasional “islands” of squamous epithelium Controversy exists in regards to the durability of these appearing with chronic PPI therapy, but the significance of repairs with at least one group suggesting deterioration in both LES pressure and endoscopic histology back toward thepresurgical level 5–6 yr postoperatively (120). A group of 55patients who had undergone laparoscopic Toupet fundopli- TREATMENT GUIDELINE VI: SURGERY
cation were studied a mean of 2.9 yr after surgery and 67%reported heartburn, 33% regurgitation, and 33% regular use Antireflux surgery, performed by an experienced surgeon, is of prescription GERD medications. On the other hand, an- a maintenance option for the patient with well-documented other group suggested that more dysphagia occurred with a full Nissen fundoplication and that the partial, Toupet fun-doplication controlled reflux with less dysphagia (121). The Level of Evidence: II
advent of a laparoscopic approach to antireflux surgery has Considerable controversy exists over the long-term effective- resulted in an increase in patient acceptance of this tech- ness of surgical intervention in GERD and whether it is equal nique (122, 123). A recent study found significantly lower or superior to chronic medical therapy. In the early-published cost and shorter lengths of hospital stay with the laparoscopic trials of medical versus surgical therapy, surgery was shown approach, although patient satisfaction was similar between to be more effective, although both trials used medical ther- the open and laparoscopic groups (124). The only adverse apy that would be considered ineffective today. The initial effect of switching from an open to laparoscopic approach comparison favored surgical over a rather modest medical appears to be an increase in dysphagia in those treated la- therapy (essentially antacids and lifestyle changes) over a 36- paroscopically (125). This approach may not be possible in month period (110). A comparison of surgery versus raniti- some patients who have had previous surgery and may be less dine and metoclopramide indicated superiority for the surgi- effective in the very obese (126). The decreased postopera- cal approach (111). The long-term outcome of many of these tive morbidity involved in this approach should not change patients reported that after 10 yr, 92% of the patients ran- the indications or evaluations for surgery, but does make this domized to medication were still on medications and 62% of option more attractive for some patients whose alternative those who were initially treated with surgery were now back would be long-term medical therapy (127). However, postop- on reflux medication (112). A trial that randomized 310 pa- erative symptoms are common and include dysphagia (128), tients between surgery and PPIs found surgery to be slightly difficulty with belching, increased flatulence, and diarrhea superior to omeprazole 20 mg per day at the end of 5 yr, but if dose titration up to 40–60 mg per day of omeprazole were Choosing a patient for surgery remains something of a used, the two treatments were equal (113). Proper selection paradox. Patients who respond fully to PPIs appear to be the and preoperative evaluation of patients is very important. In best candidates for surgery, but one wonders how advisable it a study of 100 patients, the best predictors of a good outcome is to subject a well-controlled patient to the morbidity of an- were; age <50 yr and typical reflux symptoms that had com- tireflux surgery. Some patients who are refractory to medical DeVault and Castell
therapy (especially those with nocturnal regurgitation) will esophageal sphincter pressure have not been documented and benefit from surgery, but there are not clear data to help pre- less than 35% of patients have been demonstrated to have nor- determine which patient will benefit most. An equal, perhaps malization of their intraesophageal acid exposure (measured more important factor in determining the outcome of an- with ambulatory pH testing). When the results of the available tireflux surgery is the experience of the surgeon. Many more studies (both published manuscripts and abstracts) are crit- complications and poorer outcomes occur in low volume cen- ically examined, many issues remain unresolved including: long-term durability and safety, efficacy of these proceduresperformed outside of clinical trials, and efficacy in atypical TREATMENT GUIDELINE VII: ENDOSCOPIC THERAPY
presentations of GERD, among others. Systematic reviewsof the radiofrequency (138), endoscopic sewing (139), and injection techniques (140) were unable to identify any clear Endoscopic therapy controls symptoms in selected patients indications for these techniques, but did support their use in clinical trials and outside of clinical trials in certain well-informed patients who have well-documented GERD that is Level of Evidence: III
A great deal of excitement had been generated by the in-troduction of techniques designed to control reflux endo-scopically. There are three broad categories of endoscopic TREATMENT GUIDELINE VII: REFRACTORY GERD
therapy: radiofrequency application to the LES area, tech- GERD that is refractory to medical therapy is rare. The diag- niques designed to decrease reflux using endoscopic sewing nosis should be carefully confirmed, preferably with ambula- devices, and techniques using an injection into the LES re- tory pH testing, prior to antireflux surgery. gion. Radiofrequency application (Stretta; Curon Medical,Fremont, CA) is designed to increase the reflux barrier of theLES. The open-label, 1-yr follow-up of the first cohort of pa- Level of Evidence: IV
tients treated with this technique has been recently reported The vast majority of patients will have their symptoms and (131). The symptom score related to heartburn improved ini- mucosal disease controlled with medical therapy for GERD tially in most patients and this improvement persisted. A to- (71). When a patient presents with either typical or atypi- tal of 34% of patients were back on PPIs and an additional cal symptoms of GERD refractory to therapy, the diagno- 38% were regularly taking antacids at 1 yr. A sham treat- sis should be reconsidered. This may involve an ambula- ment controlled trial has also recently been completed (132).
tory pH study, either on or off therapy, additional endoscopic Heartburn quality of life, median heartburn score, and SF 36 and manometric evaluations, and consideration of testing and physical quality of life were improved more with active treat- therapeutic trials for other conditions that may produce symp- ment compared to sham therapy. On the other hand, there were toms similar to GERD. It is also clear that some patients do no differences noted in acid exposure nor in the percentage not respond to traditional, approved doses of PPIs and that of patients who were able to discontinue daily medications increasing the dose and particularly dosing the medication (47% after active treatment, 37% after sham treatment, NS).
twice daily is appropriate in those patients (78). Refractory Reported complications have included: death (two early in the GERD is often used as a rationale for antireflux surgery and experience with the technique), perforation, and hemorrhage.
even for the development of some of the endoscopic tech- Results of the endoscopic sewing techniques have also niques. The available data suggest that patients who do the been reported. Six months after treatment with the first en- best with surgery are those who previously responded to med- doscopic sewing device (Endocinch; Bard, Murray Hill, NJ), ical therapy, not the refractory patient (114). The endoscopic 62% of 64 patients in the initial report were off PPIs (133).
techniques have not been adequately studied in patients who Extended follow-up of a small number of these patients (39) has been presented as an abstract, which suggested that lessthan 25% of patients were able to remain off medications for2 yr (134). Most recently, early data from the full thick- AREAS IN NEED OF ADDITIONAL STUDY
ness plication device (NDO Surgical, Mansfield, MA) have GERD has been extensively studied and we continue to see been reported with 74% of 64 studied patients able to be off a steady improvement in our understanding of the condition.
PPI therapy at 6 months (135). Finally, injection of a nonre- Despite this, many questions remain to be answered, includ- sorbable polymer (Enteryx, Boston Scientific, Natick, MA) has been reported to control GERD symptoms and allow 74%of patients to discontinue PPI therapy at 6 months and 70% (i) Will impedance monitoring and “tubeless” pH monitor- to discontinue at 12-month follow-up (136, 137).
ing change our approach to subsets of GERD patients? All of these techniques seem to produce an improvement (ii) Will esophageal manometry prior to antireflux surgery in reflux symptoms, although significant changes in lower be abandoned or perhaps be replaced by impedance Updated Guidelines for Diagnosis and Treatment of GERD
testing? If motility testing is abandoned, will a partial 10. Rex DK, et al. Screening for Barrett’s esophagus in or complete fundoplication become the operation of colonoscopy patients with and without heartburn. Gas- 11. Vincent ME, Robbins AH, Spechler SJ, et al. The reticular (iii) How will the availability of OTC and generic PPIs pattern as a radiographic sign of Barrett’s esophagus: An change the face of GERD for both primary care and assessment. Radiology 1984;153:333–5.
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(vi) There are many questions related to Barrett’s esopha- 14. Creteur V, Thoeni RF, Federle MP, et al. The role of single- gus covered extensively in other guidelines, but some of and double-contrast radiography in the diagnosis of reflux esophagitis. Radiology 1983;147:71–5.
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ized, double-blind, placebo-controlled study of efficacy and troenterology, 4900 B South 31st Street, Arlington, VA 22206-1656.
safety. Am J Gastroenterol 2001;96:27–34.
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