Gastroparesis and Functional Dyspepsia, Part 2: Diagnosis and Treatment

In part 2 of this podcast, Doctors Lacy, Cangemi, and Koch delve into the challenges of making a firm distinction between these two conditions.

Brian Lacy, MD, is a professor of medicine from the Mayo Clinic in Jacksonville, Florida, and Section Editor for Stomach and Small Bowel Diseases and Disorders for the Gastroenterology Learning Network. Kenneth Koch, MD, is a professor of medicine from Wake Forest University Medical School in Winston-Salem, North Carolina. David Cangemi, MD, is an assistant professor of medicine from the Mayo Clinic in Jacksonville, Florida.

TRANSCRIPT:

Welcome to this Gastroenterology Learning Network podcast. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida. I'm absolutely delighted to be speaking today to Dr. Ken Koch and Dr David Cangemi. Today, we’re going to discuss how functional dyspepsia and gastroparesis may not be that distinct and different condition we once believed they were.

Ken, going back, we're hearing this theme that for years, clinicians believed that functional dyspepsia and gastroparesis were completely separate, completely different camps, different definitions, different causes, even different treatments.

Now, clearly, the lines are blurring. You've been so involved in this gastroparesis consortium over the years. Could you highlight maybe 2 or 3 key findings from the consortium about how things are really more of an overlap and more of a spectrum rather than individual disorders?

Dr. Koch:  Yes, thank you. A paper just came out from the consortium in Gastro. It may be in print, but it certainly electronic. Basically, we looked at hundreds of patients. I think in the end, it was over 250 patients with gastroparesis who did something that we have never done before. That is, they had their gastric emptying study repeated 1 year—48 weeks—after their initial gastric emptying study. There were almost 200 patients who had normal gastric emptying.

We did take in 20% to 30% of our patients in the gastroparesis consortium who had symptoms associated with gastroparesis, but they had normal emptying.

We had this cohort that had normal emptying. Everybody got a gastric emptying study 48 weeks later. I think the thing that struck everybody the most was in the gastroparetics, at 1-year follow-up, 40% of them actually had normal gastric emptying. We used to think people were condemned for life with the diagnosis of gastroparesis. Here, people got different treatments. It's a little bit muddy. They were all at 6 different sites, doctors trying to get them better. But when they came to the actual gastric emptying, that many were normal. Overall, symptoms on the GCSI didn't change that much as an average, but when you looked at individuals, symptoms were no different. That is compared to baseline.

The 40% who had a normal emptying at 48 weeks, their GCSI symptoms were no different than at baseline when they had delayed emptying. This brought up the point then, where are these symptoms coming from? It's not just the rate of emptying. For many years now, we have many papers — there could be a dozen papers now — that show the rate of emptying does not correlate well with the symptoms.

The symptoms are predominantly in the first half hour or hour after people eat.  Interesting, it was also almost the same amount, maybe 37% who had normal emptying at baseline actually had delay.

Some of these patients with the symptoms we've been talking about are on a borderline between delay and nondelay. It doesn't even matter if they were mildly delayed, moderately delayed. This was the big message of this paper. Also, there are some full-thickness biopsies in both the delayed and the FD patients. Both small subsets of these patients that were biopsied had depleted ICCs.

Something that holds them together, you see in my mind, is the loss of ICCs. It's the loss of pacemaker cells. There are other factors like the pylorus, which wasn't studied.

The point is that these symptoms are common in the 2 groups. Gastric emptying is not the key. There's loss of ICCs. That brings up dysrhythmia as a common phenomenon. That was the main gist of that consortium study that will bring on more studies that tie these 2 groups together

At this point, what holds together in my mind are the loss of ICCs in both groups.

Dr. Lacy:  Ken, those are some amazing teaching points. I'm just going to highlight 2 from there. One is that when we think about treatment -- we're going to get to that in just a minute -- but necessarily accelerating stomach emptying may not improve symptoms. That's been shown time and time again, although still controversial.

And the second point is that patients may move back and forth a little bit with changes in gastric emptying. The third teaching point though maybe, make sure you do the gastric emptying scan correctly because so many places do them incorrectly.

Bad study, bad data, bad treatment outcome. Don't be afraid to repeat it, because people do change.

David, we heard a lot of great stuff there. Would you be kind enough just once again layer on some of the similarities and/or differences you think between functional dyspepsia and gastroparesis?

Dr. Cangemi:  Sure. Not to beat a dead horse, but the most noteworthy similarity in my mind between functional dyspepsia and gastroparesis is that the symptoms themselves, which are essentially the same as Dr. Koch just mentioned. Both can present with early satiety, postprandial fullness, abdominal pain, nausea, bloating, one of these or all of these.

In addition to the findings from the recent consortium findings, Brian, your study from a few years ago is worth highlighting where you use the Gastroparesis Cardinal Symptom Index or the GCSI to assess functional dyspepsia symptoms. Essentially, it found that the GCSI, which is validated and widely used in research studies for gastroparesis, was not able to reliably distinguish between functional dyspepsia and gastroparesis.

Talking about etiology, I think the fact that both functional dyspepsia and gastroparesis can occur as a result of an infection, the fact that there's a postinfectious group, link san important similarity between these two.

Talking about pathophysiology, as we've already talked about, the fact that delayed gastric emptying is a defining feature of gastroparesis, but the idea that a good percentage of patients with dyspepsia can have mildly delayed gastric emptying and also impaired accommodation. There are some pathophysiologic links as well between these two disorders.

Dr. Lacy:  David, that's great. I just want to highlight 1 thing there. A common misconception is that gastroparesis patients don't have pain, but as we've just heard from 2 experts, the data shows about 90% have pain. This is a neuropathic process.

David, when you think about a practicing gastroenterologist, are there 1, or 2, or 3 key points that a clinician should pay attention to when trying to determine if a patient has gastroparesis or functional dyspepsia?

Dr. Cangemi:  Absolutely. The fact that symptoms cannot distinguish these 2 disorders. That's important for everyone to recognize. You can't tell dyspepsia from gastroparesis based on symptoms alone.

Two would be to think about risk factors, as Dr. Koch mentioned. If a patient has gastroparesis, why do they have gastroparesis? When you're seeing a patient in the clinic, they have diabetes or other medications? What's their surgical history? Is there a reason why they would have gastroparesis if this is a diagnosis that you're considering?

In terms of functional dyspepsia, are there psychologic factors? Is there a history of central sensitization syndrome, or fibromyalgia, or IBS, which might make a diagnosis of functional dyspepsia more likely in your patient?

Finally, it's important to highlight the importance of the gastric emptying study to distinguish, if you're trying to make a diagnosis, tell a patient, "You have gastroparesis, or "You have functional dyspepsia." You really need a gastric emptying study. Again, as we've touched on, this might be part of the same spectrum of disease. Maybe, that may not matter as much as it used to.

Dr. Lacy:  David, great. Thank you. Ken, as we start to wind down here, what our clinicians want to know who are listening in today is if you focus on gastroparesis, could you lay out a treatment pathway? How do you do it at Wake Forest?

Dr. Koch:  One of the things that is important still is to know the rate of emptying. I agree with David. It's good to know if there is a delay, it's not the whole enchilada, but it is a marker.

For years, we've looked at the stomach's electrical rhythm with what's called the electrogastrography. It's a noninvasive EKG of the stomach, I tell patients. We've been interested in recording the normal rhythm or dysrhythmias. I think over the last 10 years, we've learned so much more about the ICCs that it's made me feel better about trying to interpret the electrical rhythm. We know so much more about it. And here's the interesting thing. About 20% of my patients who have gastroparesis have a normal rhythm. Some have a hypernormal. It is unbelievably beautiful, normal 3-cycle-per-minute rhythm.

One of the older papers — again, out of Mayo — actually shows histologically it is about 20% of patients with gastroparesis who have a normal number of ICCs. These are a little bit buried in some papers. What's going on with those patients? Many years ago, we had a paper that described that very scenario, the lay down, beautiful 3-cycle-per-minute, which means you must have enough ICCs.

My patients all had overlooked pyloric stenosis. We don't miss that so much anymore. Imagine a stenotic pylorus, but a pretty healthy corpus antrum. It's beating away at 3 per minute against an obstruction. Those people all end up having Billroth Is, Billroth IIs. They couldn't be dilated.

What we're really finding now with EndoFLIP is a lot of these patients are going to have poorly distensible pylori.

So my practice is to find those who have delayed emptying and normal rhythm. I'll say, "My gosh, I'm happy to see this because you're the person I'm going to balloon dilate the pylorus, you're the person I'm going to put the Botox into."

We have a paper on that, but we've also taken a few of those patients on to pyloroplasty, but only after I've seen 2 or 3 really, really dramatic responses. This gets at a growing interest, what is the pylorus contributing in the gastroparetic patient?

As you subtype gastroparesis, this might help our therapies. At least that's how I'm using it here at Wake. Alternatively, 75%, most patients have a dysrhythmia of some kind. Everybody manages to empty some. How do they do that? They don't have zero ICCs. There's some corpus antral contraction. The pylorus is a variable we have to figure out, but those are the patients, that's a tougher group-.

I'll try the drugs that we all have, which are very few. I must say I spend more time on diet.

Dr. Lacy:  This is a great overview. Ken, as we wind down, that low-residue diet, there's one published study in the American Journal of Gastroenterology from Magnus some years ago, it's been under study. Then, this litany of medication options, although no validated treatment algorithm. Maybe, we should just say we'll focus on individualized medicine for these patients. Right?

Dr. Koch:  That's it. For instance, we use a water load. They have 5 minutes to drink, so they're completely full. Some of my patients cannot drink 8 ounces, and they're completely full. Others can go up to 600, 700. I guess, that fundic-gastric accommodation or hypersensitivity, you tailor the diet to the gastroparesis diet.

And drugs, my gosh, it's still a problem. I still stock Reglan. I'm still going back to some bethanechol now and then. None of the great studies -- as you know, there wasn't a really beautiful, modern prokinetic study. I think it’s probably more subtle than...A prokinetic isn't going to help you if you've already got a great rhythm, but your pylorus is the problem. Prokinetic is not going to help.

As we know more patho-psy, we'll be smarter about meds, but I think we still have to try these prokinetics. I like a little bit of Mestinon. Then, it's the antinauseants that we all...Some ondansetron. We studied aprepitant in the consortium, and it seemed that it did cut down on nausea. It cut down on some dysrhythmia. But it's hard to get that drug for a lot of patients. It's expensive, and they often reserve it for the cancer chemotherapy patients. All the way up to a gastric simulator and GJ tubes for the people who are just...Their stomachs are so bad, they cannot support nutrition. It is a management smorgasbord.

Dr. Lacy:  Highlighting that, although we speak of gastroparesis as a single disorder, it's a very heterogeneous disorder encompassing both sensory and motor dysfunction.

David, in the last minute here, if you think about functional dyspepsia, can you highlight some of the treatment options that you think are most important for our listeners?

Dr. Cangemi:  Of course, so again, another long discussion, but we'll highlight. Number 1 is first to explain the diagnosis and reassurance to the patient. That goes along the way.

A lot of patients, we're seeing them for their fifth or sixth opinion. They're looking for a diagnosis. Often, many of them think that there's something sinister cause underlying their symptoms. Confidently diagnosing functional dyspepsia, explaining what that is, goes a long way.

I think the ACG guidelines, as far as treatment, put out a nice algorithm. First, looking for H. pylori, knowing that that's a risk factor for functional dyspepsia. If a test is positive, whether it's a gastric biopsy or stool antigen, or breath test, treat and then reassess. If symptoms persist, a trial of PPI therapy is reasonable as a short-term trial, once daily, maybe up to 4 weeks or so, maybe a small percentage of patients will respond to that.

When you move beyond that, and especially if the symptoms are moderate or severe, I'm often going on to use a neuromodulator.

For epigastric pain syndrome, where the pain is the predominant symptom, I often use TCAs, whereas if a patient has more meal-related satiety or fullness, I think about used in mirtazapine or buspirone because there is some small data suggesting that these medications can be helpful for those 2 subtypes.

Finally, I think in patients, especially those who have severe symptoms in concomitant anxiety and other psychological factors, I think psychotherapy can go a long way, either in isolation, but more often in combination with medications and other things to help with symptoms.

Those are things like cognitive behavioral therapy, maybe acupuncture, hypnotherapy. The number need to treat on these therapies is 4. It's very safe and a reasonable thing to do, especially if the patients are struggling.

Dr. Lacy:  David, great. For our listeners today, we can't thank you enough for joining us. You've heard this amazing state-of-the-art review on functional dyspepsia and gastroparesis.

Ken Koch from Wake Forest, thank you so much for your expert contributions to the field over the last several decades with hopefully decades to come. David Cangemi from Mayo Clinic, thank you again for your expertise and some neat cutting-edge research coming from your lab. To our listeners, thank you. To both of our speakers today, thank you so much for doing this.

Dr. Cangemi:  Thank you very much. It's a pleasure.