Gastroesophageal reflux disease, or GERD, is defined by the Montreal Classification as “a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications.” This characterization has always been intentionally broad, as symptoms of GERD can vary widely in patients, and the frequency of symptoms does not necessarily correlate with the quantity of reflux in an individual patient. To further complicate matters, only certain patients have long-term esophageal injury from GERD. Progression of GERD to Barrett’s esophagus and even esophageal adenocarcinoma can occur, but the majority of patients with GERD do not develop these long-term sequelae. In patients without concerning esophageal injury, and accumulating data on the potential risks of long-term proton pump inhibitor (PPI) therapy, how are we to think long-term about their reflux disease? If the symptoms are not able to be managed with dietary and lifestyle changes alone, should we now be considering alternative medical and procedural therapies in more of our patients?
To have a chance to answer these questions, I believe it is vital to step back and ask: why does my patient have GERD? Sometimes, the answer is obvious: it could be a recent dietary change or weight gain, or a clear anatomic process at the esophagogastric junction (EGJ) such as a hiatal hernia. However, if the cause is not obvious, further evaluation of the mechanisms of GERD in a patient can be important. The attention and interest in the pathophysiology of GERD has been increasing in recent years. For example:
-Without a hiatal hernia, traditionally it has been unclear whether a low pressure lower esophageal sphincter (LES) may have a role in contributing to worsening GERD. In addition, with the advent of high-resolution esophageal manometry studies, other LES metrics, one being the “EGJ contractility integral,” are being deciphered to study the EGJ comprehensively. Still other technology, with impedance planimetry, is being studied to assess the compliance of the LES in patients with GERD.
-There is a body of literature suggesting that the LES may shorten over time, and this decreasing LES length may be a surrogate for progression of GERD. Here too, esophageal manometry may be beneficial in determining the primary underlying cause of GERD.
-Transient LES relaxations have been a known mechanism of GERD for many years. However, the majority of evidence suggests that the quantity of these relaxations may not be the most significant factor, and GERD patients instead will likely reflux more when the relaxations occur. Thus, the physiology of the proximal stomach may have a function in GERD, and indeed an “acid pocket” has been described at the EGJ from which reflux can originate after a meal. The location of this reservoir may vary amongst patients.
There are many potential mechanisms for GERD, and these are but a few that have received recent attention. Work to decipher the major etiologies of GERD in patients is encouraging, and eventually we can hope for different “phenotypes” of GERD patients based on mechanisms.
Importantly, we know that an overall balance of symptom triggers (causticity of gastric contents, volume of reflux) and symptom modulators (ability to clear reflux, tissue sensitivity) exist to create the condition of GERD. There are a variety of technologies now that attempt to quantify reflux in patients and correlate that reflux to particular symptoms (wireless pH as well as catheter-based pH and impedance-pH testing), and even focus on the chronicity of reflux in an individual patient (mucosal impedance testing). Further study of these technologies is expected to improve our categorization of GERD patients. Lastly, our options for treating GERD continue to widen, at the same time there is increasing physician and patient concern over long-term potential adverse consequences of PPIs. There are several modern procedural options for treating GERD, with both endoscopic and laparoscopic approaches emerging in recent years.
So how should I treat my patient with GERD on long-term PPI? My approach has always been: if there is no clear indication for indefinite PPI, the goal should be to decipher if there is a therapeutic option that will allow the patient to stop it. This may be a dietary, medical, endoscopic, or surgical approach. Thinking long-term about GERD coincides with considering its mechanisms. In the current landscape, a meticulous individualized approach to care, with a concise discussion on the risks and benefits of both medical and procedural therapies for GERD, is warranted.
As we improve our ability to categorize and “phenotype” patients with GERD, as well as use our motility, pH, and impedance technologies to assess GERD in individual patients, carefully done studies should allow us to develop appropriate diagnostic and treatment algorithms. Certainly, not every patient with GERD will be expected to improve with an LES augmentation procedure, but the goal will be to answer: which patients should get which procedure? As of now, we know that the patients that do best with LES surgery are also the patients who respond best to PPI. We have to do better than that. In the coming years, I expect that we will.
Director, Center for Esophageal Disease
NYU Langone Medical Center