Antireflux surgery in the proton pump inhibitor era
ABSTRACTAlthough proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.
KEY POINTS
- If a PPI in twice-daily doses fails to relieve GERD symptoms, a pH study combined with multichannel intraluminal impedance testing can help in deciding whether to try surgery.
- Antireflux surgery can be considered for erosive esophagitis that does not resolve with drug therapy, for volume regurgitation (particularly if it occurs at night or if there is a risk of aspiration), and for patients who need lifelong treatment for reflux but have had a serious adverse event related to PPI therapy.
- Studies are needed to directly compare medical and surgical therapy in patients with extraesophageal manifestations of GERD and refractory symptoms, a difficult group of patients.
- Drugs that inhibit transient relaxation of the lower esophageal sphincter are under investigation, as are minimally invasive procedures to manipulate the physical barrier to reflux.
IF PPIs FAIL, FURTHER TESTING NEEDED
But many patients who take PPIs still have symptoms, even though these drugs suppress acid secretion and heal esophagitis. In fact, symptoms completely resolve in only about one-half of patients with erosive disease and one-third of those without erosive disease.21
Reasons for an incomplete symptomatic response to PPIs are various. Acid reflux can persist, but this accounts for only 10% of cases.29 About one-third of patients have persistent reflux that is weakly acidic, with a pH higher than 4.29. However, most patients with persistent typical GERD symptoms do not have significant, persistent reflux, or their symptoms are not related to reflux events. In these cases, an alternative cause of the refractory symptoms should be sought.
Further diagnostic testing is indicated when symptoms persist despite PPI therapy. Upper endoscopy will reveal an abnormality such as persistent erosive esophagitis, eosinophilic esophagitis, esophageal stricture, Barrett esophagus, or esophageal cancer in roughly 10% of patients in whom empiric therapy fails.10
Although patients with persistent symptoms have not been enrolled in many randomized controlled trials, a multivariate analysis showed that failure of medical therapy heralds a poor response to surgery.30 Data such as these have led most experts to discourage fundoplication for such patients now, unlike in the pre-PPI era.
pH and intraluminal impedance testing
However, this recommendation against surgery is not a hard-and-fast rule.
In patients with esophageal regurgitation, most will not achieve adequate relief of symptoms with PPI therapy alone.34 The therapeutic gain of PPI therapy vs placebo averaged just 17% in seven randomized, controlled trials, more than 20% less than the response rate for heartburn.34 This is likely because of structural abnormalities such as reduced lower esophageal sphincter pressure, hiatal hernia, or delayed gastric emptying. Antireflux surgery can correct these structural abnormalities or prevent them from causing so much trouble; however, the presence of true regurgitation should first be confirmed by MII testing. If regurgitation is confirmed, antireflux surgery is warranted, particularly in patients with nocturnal symptoms who may be at high risk of aspiration. With careful patient selection, regurgitation symptoms improve in about 90% after surgery.2
In patients with heartburn, if esophageal acid exposure continues to be abnormal on MII-pH testing, then an escalation of therapy may improve symptoms, particularly if symptoms occur during reflux or if they partially responded to PPI therapy. Options in this scenario include alteration or intensification of acid-suppressive therapy, treatment with baclofen (Lioresal), and antireflux surgery.18,35,36 In randomized controlled trials of patients whose symptoms partially responded to PPIs, antireflux surgery has performed similarly to PPIs in terms of improving typical GERD symptoms, particularly regurgitation.27,37–41 Although this scenario is a reasonable indication for antireflux surgery, recommendations should be made with appropriate restraint since it is not easily reversible, some patients experience complications, and up to one-third will have no therapeutic benefit.30
Nonacid reflux. In some cases, MII-pH testing during PPI therapy will reveal reflux of weakly acidic (pH > 4) or alkaline stomach contents, often called “nonacid reflux.”29 Nonacid reflux is often present in patients with esophagitis that persists despite PPI therapy, indicating that even weakly acidic stomach contents can injure the mucosa.42 Since intensifying the acid-suppressive therapy is unlikely to improve these symptoms, antireflux surgery may have a role.
In one study,43 nonacid reflux was well controlled by laparoscopic Nissen fundoplication, although 15 (48%) of 31 patients had persistent symptoms of GERD after surgery. No patient had a strong symptom correlation with postoperative reflux events, suggesting an alternative cause of the persistent symptoms. Therefore, antireflux surgery for nonacid reflux should be limited exclusively to patients with strong symptom correlation, and even then it should be considered with restraint, given the limited evidence for benefit and the potential for harm.
If testing is negative. In studies investigating the diagnostic yield of MII-pH testing, more than 50% of patients who had refractory symptoms had a negative MII-pH test.29 In such situations, when the symptoms are strongly correlated with reflux events, the patient is said to have “esophageal hypersensitivity.” A few small studies have suggested that such patients may benefit from surgery, but these data have not been replicated in randomized controlled trials.32
When the testing is negative and there is no correlation between the patient’s symptoms and reflux events, the patient is unlikely to benefit from antireflux surgery. Care of these patients is beyond the scope of this review.
SURGERY RARELY IMPROVES COUGH, ASTHMA, OR LARYNGITIS
GERD has been implicated as a cause of chronic cough, asthma, and laryngitis, although each of these has many potential causes.44–46 Despite these associations, the evidence for therapeutic benefit from antireflux therapy is weak.
PPI therapy shows no benefit over placebo for chronic cough of uncertain etiology, but some benefit if GERD is objectively demonstrated.47 Laryngitis resolved in just 15% of patients on esomeprazole vs 16% of patients on placebo after excluding patients with moderate to severe heartburn.48
In a large randomized controlled trial in patients with asthma, there was no overall improvement in peak flow for the PPI group vs the placebo group, although significant improvement occurred in patients with heartburn and nocturnal respiratory symptoms.46
Potent antisecretory therapy seems to improve extraesophageal symptoms when typical GERD symptoms are also present, but it otherwise has shown little evidence of benefit.
The evidence for a benefit from antireflux surgery in patients with extraesophageal GERD syndromes is even more limited. Although one systematic review49 found that cough and other laryngeal symptoms improved in 60% to 100% of patients with objective evidence of GERD who underwent fundoplication, virtually all of the studies were uncontrolled case series.49
The lone randomized controlled trial in the systematic review compared Nissen fundoplication with ranitidine (Zantac) or antacids only for patients with asthma and GERD, and found no significant difference in peak expiratory flow among the three groups after 2 years. However, asthma symptom scores improved in 75% of the surgical group, 9% of the medical group, and 4% of the control group.50
In a study that was not included in the prior systematic review, patients with laryngopharyngeal reflux unresponsive to aggressive acid suppression who subsequently underwent fundoplication fared no better than those who did not.51
Thus, based on the available data, antireflux surgery is only rarely indicated for extraesophageal symptoms, especially in patients who have no typical GERD symptoms or in patients whose symptoms are refractory to medical therapy.
