So, our next talk is by Dr. Thota, and she is going to talk about, is it good? How can you prove it? Which test? When? And she'll provide us with a summary of her approach to the diagnostic testing for gastroesophageal reflux disease. Thank you, Prashanthi. Thanks, Prasad. Good morning, everyone. In this talk, I'm going to discuss about the definitions for gastroesophageal reflux disease, and then talk about the different tests available for diagnosing or treating gastroesophageal reflux disease. These are my disclosures. So gastroesophageal reflux disease is mainly a clinical diagnosis. So I present a case scenario here. This is a 46-year-old male with a three-year history of substernal burning throughout the day as well as at night, rarely during the meals, and has foot sticking with solids. He regurgitates frequently, and he has exertional chest pain. How many of you think that he has gastroesophageal reflux disease? Here is another patient, a 42-year-old male with trouble swallowing solids, not with every meal, but frequently has rare chest discomfort later in the meals, has heartburn once a week, no history of impactions, has allergies to pollen and ragweed, and has lactose intolerance. So the former patient is somebody with echolacea. Patients frequently get diagnosed with gastroesophageal reflux disease, have the diagnosis for several years before they get accurately diagnosed with echolacea. This is a patient with eosinophilic esophagitis. So, what is gastroesophageal reflux disease? It has different phenotypes, so a common definition is difficult. A broad definition would be that it is a condition in which the reflux of gastric contents into the esophagus results in symptoms and or complications. So, that is a clinical definition, and then a GERD is objectively defined by the presence of characteristic mucosal injuries seen on the endoscopy, for example, esophagitis, or abnormal esophageal acid exposure demonstrated on reflux testing. So, there are several tests for making a diagnosis of gastroesophageal reflux disease. However, most of these tests are not usually necessary to make a diagnosis. Diagnosis is made based on the presence of typical symptoms of acid reflux or regurgitation, and then by the heartburn. So, heartburn is a retrosternal burning sensation, and then acid reflux is a regurgitation of food or acid up into the throat. Here, this slide shows all the different types of tests or measures we have for gastroesophageal reflux disease. So, most guidelines recommend, and it is a common practice too, to use PPI trial as a diagnostic test for gastroesophageal reflux disease. However, it is not very accurate. Now, here is an elegant study, and these are the patients diagnosed with gastroesophageal reflux disease based on the typical findings on the endoscopy or showing an abnormal acid exposure on the pH testing. Among these patients, approximately 70% responded to PPIs, and about 30% did not respond to PPIs. And on the other hand, patients who were not having any gastroesophageal reflux disease, that is, endoscopy is normal, and then the pH test is normal, and about 51% responded to the PPIs, and about half of them did not respond to the PPI therapy. So, what does this tell you? That there is a significant placebo effect with the PPI treatment. So, here is a compilation of different studies to see to what extent PPIs contribute to the therapeutic effect and what extent it is because of the placebo effect. The yellow color you see is the placebo effect, and then the blue is the therapeutic gain from using PPIs. So, the maximum benefit you see is in healing of the esophagitis, and on contrast, in improvement of some atypical symptoms such as hoarseness or chronic cough, it mostly seems to be because of the placebo effect. On the endoscopy, what can you see on the endoscopy, as Dr. Iyer has pointed out in so many nice pictures, vivid pictures or so? We may see the erosions, and then grade A esophagitis is not a diagnostic of GERD alone. It can be seen in about 8% of asymptomatic controls. Grade C and grade D are virtually diagnostic of abnormal pH exposure. And then second thing is look for the presence of the hiatal hernia on the endoscopy and also the battered esophagus. A long-segment battered esophagus is almost 100% associated with abnormal acid exposure. Look for peptic strictures, and then also to exclude other diseases, especially in patients with dysphagia or so. One is oesophilic esophagitis, where you see those typical rings, multiple rings within the esophagus, the longitudinal ferose or the exudate, and then echolacea. So, in echolacea, you'll see probably a foot bolus within the esophagus, a tight gastroesophageal junction, but with no mass, and then the scope goes to the gastroesophageal junction with the pop effect. And then finally, cancer, where we can see a mass. While coming back, look at the proximal esophagus, where you look for the inlet patch. Inlet patch is sometimes associated with atypical symptoms, such as hoarseness, global sensation or so. And in the case series, treating the inlet patch with radiofrequency ablation seems to help in improving the atypical symptoms. So, here is patients with various manifestations of gastroesophageal reflux disease, and how many have an abnormal pH study. In patients with NERD, which is a non-erosive reflux disease, abnormal pH testing can be seen in approximately 50% or so. And then you may ask, how is the diagnosis made? The diagnosis is made mainly based on the clinical symptoms of typical heartburn and acid regurgitation. And then in patients with erosive esophagitis, approximately 80% may have abnormal pH tests. And when it comes to battered esophagus or so, it approaches about 95 to 98% of patients have abnormal pH tests. So, if there is any contemplation for fundoplication, if a patient has a long segment battered, there is no reason to do a Bravo test or a 24-hour pH test. What is the average acid exposure time? Normal is something less than 4% of the 24 hours, and then abnormal is something over 6% of the 24 hours. Between 4% and 6% abnormal pH is equivocal, so it depends on the clinical symptoms or findings of erosive esophagitis or so on the endoscopy. As normal healthy volunteers, it is less than 4%. When it comes to erosive esophagitis or short segment battered esophagus, the percentage of time with acid exposure in the esophagus is probably about 8% to 12% or so. And when it comes to the long segment battered, we are seeing upwards of 20% or so. Typically, we don't need to do biopsies when a patient presents with gastroesophageal reflux disease alone, and then what may we see when we do the biopsies? These are the typical histologic features. There may be papillary elongation, there is basal cell hyperplasia, and then the dilated intercellular spaces, which is diagnostic of gastroesophageal reflux disease. However, a good thing to know is this microscopic esophagitis is not very sensitive or specific for gastroesophageal reflux disease. You may see microscopic esophagitis in up to 75% of patients with non-erosive reflux disease, and then up to 65% of patients with reflux disease, I'm sorry, with reflux hypersensitivity. And it can also be seen in up to 15% of patients with a functional heartburn or so, and the same in healthy volunteers. So this is not necessarily specific for gastroesophageal reflux disease. So as we go along the spectrum of the disease, we start seeing that the intercellular space diameter increases. The most widely used tests for diagnosing gastroesophageal reflux disease is the pH monitoring. This helps us to calculate the amount of acid exposure in the esophagus, one, and then the second thing is it also helps us to see if there is any symptom association, to see if the patient's heartburn or regurgitation are related to reflux or not. So what are the different modalities available for pH monitoring? The oldest is a 24-hour pH catheter, which goes through the nose and it is placed five centimeters above the lower esophageal sphincter. The second one, the one which came about in the past 20 years, is the Bravo test, which is a 48-hour wireless capsule for pH monitoring, and it can be used for extending the monitoring for 96 hours too, to see what the response to the PPI is. An improvement over both is a 24-hour multi-channel pH impedance catheter. What is the advantage of this? The advantage of this is the previous two, we can measure only the acid exposure, but with the impedance catheter, we can see if there is any weakly acid reflux episodes or the non-acidic reflux episodes, which are contributing to the patient's symptoms, for example, patients taking PPI therapy. A recent development is a mucosal impedance testing. The advantage of this is it's an endoscopically placed catheter and you can get instantaneous readings during the endoscopy. The next one is a pharyngeal pH monitoring to see if there is any LPR going on, but it is not sensitive or specific or reproducible to be of any use for diagnosing LPR. And finally, there is a salivary pepsin. Presence of pepsin is indicative of reflux coming up to the throat. It is sensitive, but not very specific for diagnosing laryngopharyngeal reflux. On the right-hand side, you're looking at a 24-hour pH tracings. So here is the pH. The pH is approximately seven or eight throughout the testing. So this is not good. Whereas here in the bottom right corner, you see the reflux episodes highlighted in red. So this is the time. And from this, we can measure the amount of time the esophageal pH is less than four in that 24-hour period. So this is a tracing of an abnormal acid exposure. So going on to the impedance testing, a couple of things to remember is the impedance, when there is a liquid bolus passing through, that leads to reduction in impedance. When there is a gas bolus passing through, there is an increase in impedance. So this helps us to figure out whether we are dealing with belching or acid reflux. And then we are also looking if there is antigrade movement or retrograde movement. So retrograde movement of liquid is acid reflux or gastric reflux. Antigrade movement of a liquid bolus is with swallowing. Retrograde movement of a gas bolus is belching. So here is an impedance test of an acid reflux episode. On the left-hand side, you're looking at the pH tracing. You see that the pH drops below four. So this is an acid reflux going on. Now the impedance catheter has multiple sensors throughout. And when you look at here, here is a reflux starting first. So there is a decrease in the impedance first happening in the distal sensor, and then moving up as it goes proximally. So this is an acid reflux episode happening. Here is an example of a non-acid reflux episode. The pH is about four. So you don't see if you just do a pH testing, you may not notice this, that there is any reflux going on. And here is the impedance with a non-acid reflux. And here you see the decrease in the impedance starting first in the distal sensor, and then it going approximately a fall in the impedance as it goes proximally. So this is a non-acid reflux episode. And here is an example of the gas reflux. pH stays the same, no change in the pH. As I mentioned before, when there is a gas bolus passing through, there is an increase in the impedance as opposed to a decrease in the impedance that we see with liquid bolus passing through. So it is starting in the distal sensor and moving up proximally. So it starts in the distal sensor first, and you see there's a gradual increase in the impedance as it goes proximally. So this is an example of a gas reflux or belching. So what is normal and abnormal? So this shows the different studies highlighting the normal, upper limits of the normal, and then the abnormal. And all those in the pink are the normal, and then all those in the other colors, the green and the blue, are the abnormal. So based on this multiple studies, the Lyme's consensus have come up with the normal as anything less than four, and abnormal as something more than 6% of the time. And between four and six is equivocal, and depending on the other signs or symptoms to make a diagnosis of good. So when you look at the impedance test, and this gives the number of reflux episodes in healthy volunteers and in patients with non-erosive reflux disease, and then patients with erosive esophagitis. In healthy volunteers, the median is 21 to 32 in different studies. In patients with non-erosive volunteers, the median is 21 to 32 in different studies. In patients with non-erosive reflux disease, it is between 53 to 57. And then in erosive esophagitis, about 73 or so. So based on this, the criteria for making a diagnosis of what is abnormal and normal impedance is between 40 and 80. So anything less than 40 reflux episodes is considered as normal, and more than 80 episodes is considered as abnormal, and between 40 to 80 is equivocal. So recently, there are some two novel parameters described on the pH impedance study, which are more sensitive than the acid exposure times. So one is called as a post-reflux swallow-induced peristaltic wave. Quite a mouthful, but the main thing is it is a measure of the reflux clearance from the esophagus. So whenever there is reflux coming up into the esophagus, that simulates a secondary peristalsis, which pushes the acid down. So if it is not able to do that for various reasons, because of ineffective esophageal motility or so, that would lead to a longer acid exposure time and more mucosal damage. So this is the technical definition of the post-reflux swallow-induced peristaltic wave. So there is an antigrade drop in the impedance relative to the pre-swallow baseline traveling from the proximal site to the distal site. So here it is. And then this is followed by at least a 50% return to the baseline in the distal impedance site. And then it is calculated with the number of reflux episodes followed within 30 seconds by a peristaltic wave by the number of total reflux episodes into 100. So anything less than 61% is considered as abnormal. So less than 61% of the reflux episodes followed by a peristaltic wave. The other measure, other parameter, is the mean nocturnal baseline impedance. Mean nocturnal baseline impedance is measured from the distal-most sensor during the nighttime, so three 10-minute periods around 1, 2, and 3 a.m. are selected. And then with the automated analysis, we can get the mean baseline for each period. And then we exclude periods when there are any reflux episodes or pH drops happening. And then the mean of these three measurements is manually calculated to obtain the mean nocturnal baseline impedance. And then abnormal is something less than 22,292 ohms. So whenever there is any acid, as I mentioned, when there is a liquid or so staying within the esophagus, then the impedance will go down. So based on this, this gives the accuracy of the total acid exposure in the esophagus with the PSPW index and the mean nocturnal basal impedance. In erosive reflux disease, the accuracy of total acid exposure is approximately 89%, and the PSPW index is 97%, and the mean nocturnal basal impedance is about 89%. And then the accuracy in non-erosive reflux disease for total acid exposure is only 61%, whereas for PSPW index, it is 89%. And mean nocturnal impedance is about 75%. So as you see here, PSPW index is the most sensitive and equally specific as the pH acid, total acid exposure and diagnosing gastroesophageal reflux disease. And then the mean nocturnal basal impedance is complementary too. So these are the parameters to know about when we do the pH monitoring. How do you define a reflux episode? A drop in the pH below four, which lasts at least for 10 seconds or more. What is considered as a reflux episode when the pH is less than four? So this is somewhat different from what we learned in our basic chemistry lessons in high school. Weakly acidic is when the pH is between four and seven, and then non-acid is when the pH is more than seven. When is acid exposure time considered abnormal? When it is more than six and normal is less than 4% of the time in 24 hours. Number of reflux episodes on the impedance testing. Again, to recap, normal is less than 40 and abnormal is more than 80 reflux episodes in 24 hours. And then when it comes to symptom association, the reflux happening within two minute window before the onset of the symptom. So these are the different symptom indices seen in GERD patients. One is the symptom index, where, which measures the percent of reflux associated symptom episodes. Abnormal is something more than 50% of the time. And then the disadvantages are it does not take the total number of reflux episodes into account. The symptom sensitivity index is a percent of symptom associated reflux episodes. And then what is considered abnormal is more than 10% of the time. And then the disadvantage of this is it does not take the total number of symptom episodes into account. Something better than either of this is a symptom association probability. So this is to say that the symptom, the association is not due to chance alone. And then the abnormal value is more than 95%. And this is automatically calculated in the software. And then it provides a better insight into the relationship between the symptoms and the reflux. So the Bravo 96 hours extended monitoring, what it tells us is one, it helps us define if the patient has GERD or not. And then the second thing is we can see if the symptoms are responsive to, if the symptoms are responsive to PPI therapy or not, or if there are any overlap syndromes going on. So in this study about 35% of the patients had abnormal acid exposure time when the study was done off PPIs, it was, it reduced to 2% on PPIs. So 2% are truly refractory to PPIs. And then when it comes to the symptom association about 50%, 45 to 50% had a positive study off PPIs. I made it reduce to approximately 10% or so on PPI therapy. So what this would help as I mentioned is it would help one to diagnose GERD and second to see to what extent it is responsive to PPI therapy. So mucosal impedance testing. The mucosal impedance testing is like an endoscopically placed catheter. And it has two sensors at the tip where we can get the impedance values at different levels of the esophagus. And then what this does is we can see what the impedance is at various levels or so. And then a cutoff value of 2019, five centimeters above the squamous columnar junction is diagnostic of gastroesophageal reflux disease with a sensitivity of 76% and the specificity of 95% or so. As I said, the main advantage is you get instantaneous results. The patient don't have to wear the monitor for 24 hours or for 48 hours or so. It is also being used for looking at eosinophilic esophagitis where there is no change in the impedance throughout the different sensors along the different lengths of the esophagus. Whereas in gastroesophageal reflux disease, the impedance is the lowest at the gastroesophageal junction and it slowly starts increasing as we proceed proximally. In other esophageal diseases like Echolacea or so, the mean levels are much higher than what we see with gastroesophageal reflux disease. Esophageal manometry. The high resolution esophageal manometry is mainly to rule out other diseases. It is not to rule in gastroesophageal reflux disease. Now here, what we are looking at is a manometry. Think of it like a barium swallow. So here is the upper esophageal sphincter. This is the pedistaltic wave passing through the esophagus and here is the lower esophageal sphincter. And then the y-axis is the length of the esophagus. The x-axis is the time. And then the color gradient gives an idea about the pressure changes in the esophagus. So this is a normal swallow. Here we don't see any pedistalsis with a swallow. So this is absent contractility. And now here is a patient where there is a swallow. We don't see any normal pedistalsis and the lower esophageal sphincter is not relaxing. This is an example of type 2 echolacea. And then this is a patient where there is a difference between the lower esophageal sphincter. There is a distance between the lower esophageal sphincter and then the diaphragm. So this is a patient with hiatal hernia. So what are the findings we see in patients with gastroesophageal reflux disease? We may see a low lower esophageal sphincter basal pressure. And then the EGJ separation, if it is more than three centimeters, it is significant for abnormal acid exposure time and positive for symptom association, the SEP score. There is a new novel parameter to look at the EGJ contractile integral, which gives an idea about the strength of the lower esophageal sphincter muscle. And as I mentioned, the manometry will help to look for scleroderma type esophagus or echolacea. Definitely a must before you're contemplating any hundraplacation or any endoscopic therapy for gastroesophageal reflux disease. High resolution manometry is also useful to rule out rumination. So there is a voluntary contraction of the abdominal muscle. So you see an increased pressure of at least 30 millimeters above the baseline or so. And this is followed by a reflux episode that you can see on the manometry test. One of the new novel parameters, which is useful prior to hundraplacation is what is called multiple rapid swallows. So multiple rapid swallows, what we do is give a small 2 ml swallows within three seconds or so, five of them, and then wait for it. And then this is followed by a big peristaltic wave. We measured the DCI, distal contractile integral, gives the idea of the intensity of contraction. So that is the length of the contraction, then the width of the contraction, as well as the intensity of the contraction. So the ratio between this, the DCI of this wave, followed by the mean DCI of the preceding 10 swallows, it should be greater than one. Greater than one is normal. It indicates the presence of contractile reserve. It is a sensitive marker for predicting post-hundraplacation dysphagia. And the other one which will help predicting post-hundraplacation dysphagia is the presence of preoperative dysphagia. The new diagnostic test for evaluating the esophageal motility is the endoflip. So the endoflip gives an idea about the distensibility. It is not as useful in patients with gastroesophageal reflux disease. It has, there is a distension balloon, and then it is placed across the gastroesophageal junction. The main advantage is to evaluate patients with, evaluate the level of EGGA outflow obstruction or so, mainly useful for patients with dysphagia to tailor the fundoplacation or so. So what is normal at 60 cc inflation of this balloon? The maximum EGGA diameter of more than 18 millimeters and the normal EGGA distensibility index of more than 2.8 is considered as normal. So if it is less than this, or if these two are less, so that would be indicative of either a stricture or some type of constriction at the gastroesophageal junction, which would be from Echolacea or so too. So in summary, when patients have symptoms and then the refractory to PPI therapy, and if the patient never had any prior workup, this is the algorithm to follow. We can go through any of these three tests. One is the 24-hour pH test or the 24-hour pH impedance test or the Bravo test. Main thing is to do the study off medication, off PPI therapy for one week to see if the patients truly have GERD or not. So if the pH is more than 6% or if on the 24-hour pH impedance, if there are more than 80 reflux episodes, then that's diagnostic of gastroesophageal reflux disease. If there is normal amount of reflux burden, but if there is positive symptom association, that is called as reflux hypersensitivity. And if there is a normal reflux burden, patient has symptoms, but negative symptom association, that's what is called as a functional heartburn. Then in a patient with known GERD and then their refractory to the therapy, main thing to do is the 24-hour pH impedance test on PPI therapy. So if there is abnormal reflux burden, then that is persistent GERD. And then if it is positive symptom association, it is reflux hypersensitivity. And if there is normal reflux burden and negative symptom association, it may be because of functional heartburn or an alternative diagnosis. So in summary, this gives an idea about what are the conclusive or diagnostic of gastroesophageal reflux disease. Finding a grade C or grade A esophagitis on endoscopy, a bad esophagus, or a peptic stricture on the pH test and acid exposure time more than 6% or reflux episodes more than 80 in 24-hour period. Grade A and grade B esophagitis are not very specific for acid reflux disease. And then these are the equivocal findings on the pH test or the impedance testing. And then at this time, this is an evolving data about the PSPWI and then the mean and nocturnal basal impedance. And then if a patient has acid exposure less than 4% and then the reflux episodes less than 40, then that's the evidence against gastroesophageal reflux disease. So in summary, there is no 100% diagnostic foolproof test for making a diagnosis of gastroesophageal reflux disease. Diagnosis is based on symptoms as well as the objective findings. Be aware that on endoscopy, the esophagitis can be infectious or due to pill-induced esophagitis. And then pH testing can be negative in patients with erosive reflux disease, as we have seen before. In NERD, probably about 30% it is negative. PPI is not a very sensitive. PPI testing is not a sensitive test because it is a good placebo effect. And then be wary of other functional disorders, then gastroparesis, rumination, and then supragastric belching. Thank you.

diagnostic testing

GERD

reflux symptoms

complications

pH monitoring

impedance testing

high-resolution esophageal manometry