“Challenges in GORD” Session at UEG Week 2014.
“Therapy update: GORD” Session at UEG Week 2014.
“New options in gastro-oesophageal reflux disease” Session at UEG Week 2014.
Gone are the days when a doctor would diagnose gastroesophageal reflux disease (GORD) simply by asking about symptoms and/or evaluating the response to acid suppression. Though this is still the case in many clinical practices, particularly for patients who have uncomplicated symptoms, a more accurate diagnosis usually involves undertaking invasive and expensive procedures that, nonetheless, are still claimed to have only moderate sensitivity and specificity. As such, more specific, noninvasive and cost-effective methods are needed for the diagnosis of GORD.
GORD is a common and chronic condition that has a significant impact on quality of life and confers a significant economic burden. It generally arises from the reflux of stomach contents into the oesophagus, thus leading to oesophageal injury and associated complications. The most common cause of GORD is the disrupted relaxation of the anti-reflux barrier, which is composed of the lower oesophageal sphincter and the diaphragmatic crura; when failing to respond to swallowing, these transient lower oesophageal relaxations result in reflux of gastric fluid through the oesophagogastric junction. Heartburn and acid regurgitation follow. Ultimately, in some patients acid reflux may damage the oesophageal squamous epithelium and lead to the development of Barrett oesophagus. Left untreated, Barret oesophagus can progress to oesophageal adenocarcinoma.1
The European Association of Endoscopic Surgery (EAES) states that the two main GORD diagnostic tools are upper endoscopy and long-term impedance esophageal pH monitoring. Indeed, the combined information obtained from clinical symptoms, endoscopy and pH testing is usually considered to be sufficient and specific for the diagnosis of GORD. The EAES also highlight that “…further diagnostic investigations may be needed to verify functional abnormalities and establish the indication for surgery or other invasive therapies.”2 These additional diagnostic tools include high-resolution manometry (HRM), video-radiography and scintigraphy. For patients who have more severe symptoms, such as dysphagia and odynophagia, those who do not respond to acid suppression, or those in whom Barrett oesophagus is suspected, such additional diagnostic tools should be employed.3 Unfortunately, this comes at a sizeable financial cost.
In Germany, the incidence of GORD is high and the associated healthcare costs have been estimated at €4.8 billion.4 In the United States, GORD represents the most common GI-related diagnosis; annually, GORD accounts for 8.9 million patient visits to the clinic and endoscopy exams cost $32.4 billion.5 These budgets emphasize the need for alternative, cheaper diagnostic methods for GORD and, ideally, noninvasive ones. Encouragingly, we might be on the right track with two recently published studies on novel GORD diagnostic tools, namely pepsin detection in saliva and minimally invasive oesophageal mucosal impedance testing.
Several pathological settings may lead to pepsin being found in the laryngeal and paranasal sinus mucosa, saliva, middle ear effusion, tracheal secretions and bronchoalveolar lavage fluid. In their study, Hayat and co-workers sought to determine the value of salivary pepsin for discriminating patients with reflux-related symptoms from those with functional heartburn (FH).6 Pepsin was more likely to be detected in the saliva of patients with GORD and hypersensitive oesophagus (HO) and at higher concentrations than in the saliva of controls or FH patients. As such, the authors propose that salivary pepsin testing may complement GORD diagnosis.6 The fact that salivary pepsin can distinguish between GORD/HO and FH is extremely relevant, as most GORD patients benefit from pharmacological or surgical anti-reflux therapy, whereas FH patients do not. Interestingly, the detection of pepsin in saliva may also help in the diagnosis of laryngopharyngeal reflux (LPR).7 Despite the belief that LPR symptoms primarily result from GORD-related alterations of the laryngeal mucosa by gastric fluids, LPR differs from GORD in symptomatology and treatment modalities. A higher concentration of pepsin and bile acids has also been found in the saliva of patients with early laryngeal cancer than in the saliva of healthy volunteers, suggesting that LPR plays a role in the development of laryngeal carcinoma and might have utility as a disease biomarker.8
The question of how specific pepsin is for the diagnosis of GORD then arises. Indeed, is salivary pepsin diagnosing GORD, LPR or laryngeal carcinoma in development? As it currently stands, the measurement of salivary pepsin seems to represent a quick, cost-effective, noninvasive and simple 'office-based' method for GORD diagnosis, which I believe should be followed or paralleled with other disease-specific methods. Nonetheless, it holds a great value on its own in pinpointing the next step; for instance, the absence of pepsin could be taken as a sign of null or low frequency reflux events.
Ates and co-workers have developed a minimally invasive device to assess oesophageal mucosal impedance as a marker of chronic reflux in GORD, where impedance is measured close to the squamocolumnar junction.9 They found that the impedance values were significantly lower in patients with GORD, with mucosal impedance patterns being identified in patients with oesophagitis at higher levels of specificity and positive predictive values than wireless pH monitoring.9
Despite being a simple method that’s easy to use and provides immediate results, it is unlikely that mucosal impedance will fully replace current GORD diagnosis tools, as it is unable to distinguish between different GORD symptoms or even GORD-related disorders, which require different therapeutic approaches. Still, it represents an excellent strategy to differentiate between GORD and FH, much like salivary pepsin. Though measurement of mucosal impedance is still invasive, the procedure is quick, which makes it attractive for patients who cannot (or will not) tolerate a transnasal probe that must be in place for 24 hours.
Salivary pepsin levels and oesophageal mucosal impedance stand as two recent major breakthroughs in GORD diagnosis, but more are needed. I hope to see a lot of new and exciting discoveries on GORD diagnosis and management this October at UEG Week 2015! In the meantime, please feel free to browse the UEG Education Library for more resources.
References:
“Challenges in GORD” Session at UEG Week 2014.
“Therapy update: GORD” Session at UEG Week 2014.
“New options in gastro-oesophageal reflux disease” Session at UEG Week 2014.
Dr Rui Castro is currently a Principal Investigator at the Research Institute for Medicines (iMed.ULisboa), Portugal. He completed his PhD at the University of Lisbon and the Department of Medicine (GI Division), University of Minnesota Medical School, USA, in 2006. Since then, Dr Castro has been combining his background on the modulation of liver cell function with his most recent discoveries in the miRNA field, to answer key questions on liver physiology and pathophysiology, while supervising both undergraduate and postgraduate students under the GI umbrella. In 2015, he was selected as a UEG Rising Star. Follow Rui on Twitter @RuiCastroHD.
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