Introduction
DR. HENRY PARKMAN: Hello, and welcome to this program on Updates in the Management of Chronic Constipation. I'm your host, Dr. Henry Parkman, professor of medicine in the GI section at Temple University Hospital in Philadelphia.
Joining me in Philadelphia for this discussion is Dr. Ann Ouyang, professor of medicine in the Division of Gastroenterology and Hepatology at the Pennsylvania State University College of Medicine. Also joining us from Iowa City is Dr. Satish Rao, who is professor of medicine and Director of Neurogastroenterology and GI Motility at the University of Iowa.
This subject is on chronic constipation. Chronic constipation is one of the most common complaints reported by Americans. In the United States, it results in more than 2.5 million physician visits and also over 92,000 hospitalizations annually.
The definition of chronic constipation, as defined by physicians, is usually less than three bowel movements per week. However, when defined by patients, they report unsatisfactory defecation with marked difficulty with stool passage. Symptoms also include straining, hard and lumpy stools, a sensation of incomplete evacuation. Some patients also use manual maneuvers to pass the stool. In the Rome criteria, these symptoms had to be greater than 25% of the time in attempts at defecation.
The learning objectives of this program are, first, to understand the criteria for the diagnosis of chronic idiopathic constipation, to understand proper patient workup of a patient who has chronic constipation, and to understand available treatment options for chronic constipation.
Let's begin this discussion by considering the case of a 35-year-old secretary with increasing constipation for the last nine years. Satish, I'm hoping you can present your case now.
Case Presentation 1
DR. SATISH RAO: Hi, Henry, I think this is a very nice case that illustrates some of the learning objectives that you've just outlined.
This is a story about a 35-year-old secretary who presented with a nine-year history of progressively increasing constipation. The symptoms actually began during her college days, initially with a bout of constipation during, prior to an exam and then with rectal bleeding. Now, she describes a bowel movement once every one to two weeks, she describes excessive straining, spending several minutes, up to twenty to thirty minutes at times. She describes the stools are hard and pellet-like. And, occasionally, she notices some bleeding. There was no history of digital maneuvers to remove stool, but she describes a feeling of incomplete evacuation with every bowel movement.
To relieve her symptoms, occasionally, she has tried using an enema or suppository. That provided some temporary relief, but, most of the time, she remains dissatisfied with her bowel habit. She tried over-the-counter laxatives including milk of magnesia, polyethylene glycol preparations that were prescribed to her by a local physician, but none of them really has afforded any relief of her symptoms.
With regards to her past history, she has a history of migraines. She also has a history of seasonal allergies, but she denies any back injury or pelvic injury. She has never been pregnant and, currently, her drugs include Excedrin, largely for the headaches, fexofenadine for allergies, minocycline 100 mg b.i.d. for acne and she takes a nasal spray for allergies again.
Her general examination was largely unremarkable. In the abdomen, however, there was significant fullness, particularly in the lower abdomen and in the left lower quadrant with very minimal tenderness. Digital rectal examination showed that the rectum was full of hard, pellet-like stools. We took a sample of the stool which was negative for guaiac testing.
With a finger in the rectum, we asked her to attempt defecation and found that she had somewhat impaired pushing effort, but, most significantly, she paradoxically squeezed my finger, suggesting that she may have some dyssynergy or incoordination with her bowel habit.
The Differential
So with this as the history, I'm going to have my colleagues jump in and tell me what they think is the possible diagnosis. Number of things come to my mind, for example: could she have irritable bowel syndrome with constipation? Could she have slow-transit constipation or does she have features suggestive of dyssynergic defecation or normal-transit constipation? Or could it be that she has Hirschsprung's Disease that was missed? She's presenting at an adult stage with Hirschsprung's Disease.
Let me see what Dr. Henry Parkman has to say about this.
DR. HENRY PARKMAN: Satish, that is a very interesting case and it's something that, actually, in my practice, I see quite a lot; patients with a longstanding history of constipation. We try, in the history, to try to get some inklings as to what's causing the symptoms. You know, you describe the patient having straining, hard, pellet-look stools, excessive time on the commode, suggesting that there's a problem in the anal-rectal area and, possibly, dyssynergic defecation or what we what call functional rectosigmoid obstruction at Temple.
However, when the studies that have looked at "Can you diagnose this by history?" There's often a marked overlap between this disorder as well as delayed chronic transit or slow-transit constipation. And, also, irritable bowel syndrome with constipation, there's an overlap between that disorder and chronic idiopathic constipation. Some patients, including possibly this one, can, when you study them, have totally normal colonic transit.
The one diagnosis that I think would be a bit unusual in this patient would be the diagnosis of Hirschsprung's disease. Usually, the few cases I see (and we diagnose this in about one case per year at our center), they have longstanding chronic constipation, almost from birth. They always describe [that] for a while, they thought they were normal, but, when they talk to other people, they find out that having a bowel movement once every two weeks is markedly unusual.
So, by the description, this patient meets the criteria of chronic constipation and our job here is to find out what might be the subtype of constipation she might have. And it seems, by the history and physical, she most likely has dyssynergic defecation, although these other disorders like slow-transit constipation can also enter in the differential diagnosis.
DR. SATISH RAO: Let me ask Ann. You know, Ann, do you think that you probably see a lot of patients with similar kind of story. Would she merit the IBS with constipation criteria at all or is there something that's not in favor of that?
DR. ANN OUYANG: Well, I think that, from the ROME criteria, abdominal pain is a feature of irritable bowel with either constipation or diarrhea. She really doesn't complain of abdominal pain significantly. So I think she wouldn't really fall into the category of irritable bowel.
I think I agree with Henry that it's likely to be dyssynergic defecation or slow-transit constipation or a combination of those two. And I agree that, usually, also the cases we've seen with short-segment Hirschsprung's have had constipation, really, since infancy, although they may not present until early adulthood.
DR. SATISH RAO: Right. So, I think one of the things to bring up in this case is the history is quite important and, based on the historical information that we currently have, I think at least the two panelists are tending towards a diagnosis of dyssynergia and have discounted the possibility that she may have more IBS, largely because of the pain-related issues.
The Treatment Plan
Let's see what we should do next.
Now the question that arises is, with this background, should we go ahead and treat this patient. If so, how should we treat this patient? Or, as you know, she's already tried a number of over-the-counter preparations and she's failed this. Or is it the case now that we should investigate this patient and, if so, what kind of investigation should we be doing to give us some clues regarding the underlying pathophysiology? Let me begin with you, Ann, what do you think we should do? I mean, should we treat or should we investigate, and give me the options as to how you would approach this?
DR. ANN OUYANG: Well, I think she has been tried on a number of bowel regimens, milk of magnesia, the polyethylene glycol-based medications. She's been having problems for nine years and, clearly, this is becoming more of an issue for her.
I think my general philosophy is that investigations should only be done if it's going to actually change your treatment. And I think, clearly, in cases like this, differentiating between slow-transit constipation and dyssynergia significantly changes the treatment approach. So I think that that is an important differential to make.
Clearly, she should be on some treatment as you're doing this, just for patient comfort, but I think she does require further investigation. Henry, do you agree?
DR. HENRY PARKMAN: Yes, I agree. She's been on milk of magnesia and, actually, she's been on a PEG solution, polyethylene glycol, which I presume is either MiraLax or the other preparation, GlycoLax, without much help at all. She's coming to us, as a gastroenterologist, for more help and I like to try to understand what the etiology of the constipation is, because, if it's slow-transit constipation, you might try more of the prokinetic agents and, if it's dyssynergic defecation, that might improve very well with biofeedback therapy. So I think the testing is very appropriate at this stage to try to understand the underlying cause or at least part of the pathophysiology to help separate them and do different types of treatment regimes.
The Role of Colonoscopy
DR. SATISH RAO: Let me ask you, Henry, do you think that there is any place for a colonoscopy in this kind of situation or you're really interested more in just functional testing? Are you looking at just morphological testing, structural testing as well as function or mostly functional testing?
DR. HENRY PARKMAN: Well, that's a good point and we would also do a colonoscopy in the patient. I know she's only 35 years old. She's been symptomatic for nine years and it will probably be normal, although, very rarely, we can find some obstructive lesions or you can find signs that maybe she's taking other medicines that you don't know about and that you might, in some of these patients, find evidence of marked melanosis coli
So I think a colonoscopy or a barium enema is helpful for the patient also to help relieve when there's no other underlying cause. Ann, would you do a colonoscopy in this patient at her age?
DR. ANN OUYANG: Well, I think she does need some visualization of the colon, either a barium study or a colonoscopy. I think she does have rectal bleeding, which is likely to be related to hemorrhoids from her straining, but I think that that would be one of the things that we would consider in a quote, a "long feature." So I think that she should probably have some anatomic evaluation. How about you, Satish?
DR. SATISH RAO: I agree with you there. I think, you know, that one of the things we did was a systematic review published in the American Journal last year, we tried to look at the literature to see if there is evidence that would support the use of a number of investigations that we routinely do and colonoscopy was one of the ones that we did.
We found that there was no evidence to support the routine use of colonoscopy in the evaluation of a patient with constipation. You know, that was largely based, of course, on a large VA retrospective study where they compared constipated individuals with screening colonoscopies and looked at the yield of colon cancer, colitis, polyps, etc. And what they found was there was no increased yield or benefit in patients presenting with simple constipation.
But I think what you rightly point out there is the presence of any alarm features, such as bleeding or weight loss or nocturnal symptoms. If they are present or if a patient is over the age of 50, I think, you know, it changes the overall approach and I would agree, in that kind of situation, she would benefit from a colonoscopy.
So this lady did have a colonoscopy. She was found to have a couple of small internal hemorrhoids. I think what was happening was she was straining so much that those hemorrhoids were tending to bleed in the presence of hard stools and that was the cause of the bleeding. But, otherwise, no other mucosal abnormality was done.
Functional Assessments
So I take it, from our discussion, that once you've excluded any structural reasons, both of you would agree with me that we should proceed with some functional assessment. And, if so, maybe, Ann, what kind of tests would you order in your center?
DR. ANN OUYANG: Well, I would order an assessment of transit and I know, at Henry's facility, they can do a scintigraphic measurement. We don't have that option, so we would do a Sitzmark, which is a sort of kind of simpler sort of more crude, but fairly helpful, I think, way of looking at transit. We would do an anorectal manometry and probably defecogram.
DR. SATISH RAO: All right. So you would do those three tests, colon transit study, anorectal manometry and defecography to better-define the underlying pathophysiology. And Henry would probably do a more sophisticated study. Maybe, Henry, why don't you tell us a little bit about what you would do and why you would do that?
DR. HENRY PARKMAN: Sure. At our center, we have a very good nuclear medicine section. We do a test called whole gut transit scintigraphy, which is a three to four day test where we measure gastric emptying, small bowel transit and colonic transit. We do the colonic transit with imaging over three days to see if there's normal transit through the colon, if there's delayed suggesting colonic inertia or sometimes you can see a lot of the radioactivity in the rectosigmoid area suggesting dyssynergic constipation.
We do this test because we have access to it, but, also, in some of the severe cases where you might be thinking of surgery, you want to make sure that the upper GI tract motility is fairly intact. I must say, in the last year or so, I have been using a lot more of the sitzmark radiopaque marker test to look for colonic transit, because I can start the study actually the day I see the patient. I see patients on Wednesday, and I would get the abdominal X-ray on Monday, five days later, to do the sitzmark radiopaque marker transit test.
DR. SATISH RAO: All right. So what you say, though, clearly, Henry, is that Sitzmark test is more widely performed, is more easily available to us and we can interpret that more readily. The nuclear scintigraphy perhaps is a little bit more objective, more elegant study and it gives us a feel for the upper gut as well as the colonic function, but then it's not widely available, so that's a limitation of that study.
DR. HENRY PARKMAN: Yes.
DR. SATISH RAO: So, moving on with this lady here, what we did, in our center, was the three tests that we just discussed, which was a colonic transit study, anorectal manometry and a balloon expulsion study. Now, typically, we used to do a lot of defecography. We have kind of moved away from it and, generally, in most cases, with respect to dyssynergy, I don't do that, unless I need to know some other information or I suspect there is a rectocele or prolapse or some issue that's going on, largely because of the potential excessive exposure to the pelvic region and so on from ovarian and so on and most of these are young woman that we tend to see. So we've tended not to use a lot of that study, in most instances. But, selectively, we use defecography.
Let me first share with you the results of this particular lady's colonic transit study. On this panel, you can see her plain abdomen X-ray that was taken at 120 hours after ingestion of Sitzmarker capsules.
Now, the way we did the study was we gave her three different-shaped Sitzmarker capsules. On day one, she took a bisect capsule, a capsule containing 24 plastic markers with a bisect shape, not a Mercedes, just a bisect shape. On day two, she took plain ring and, day three, she took a Mercedes-Bens, or a trisect-shaped marker. These were taken on three consecutive days and, on day six (which is roughly 0120 hours) after ingestion of the first capsule, she had a plain X-ray of the abdomen taken.
And we're presenting two panels here. On the left-hand panel, you can see most of the abdomen, but the pelvic area is not clearly defined in this X-ray, so she had another panel where we can see the pelvic X-ray. What you can see is there are hardly any markers in the right side of the colon, but the left side of the colon, there are significant number of markers, all compacted together along with stool there. And, also, there are significant markers in the rectosigmoid region. So, most of the markers are held back, if you like, in the left side of her colon.
So, Henry, how would you diagnose this, if you see this kind of an X-ray in your practice?
DR. HENRY PARKMAN: Well, you have most of the markers retained on the left side, but let me just say that this is a very elegant way of doing it. A simpler way of doing it is to take one capsule with the 24 markers and then just repeat the X-ray five days later or 120 hours. And if there's more than six retained, that suggests there's abnormal transit.
In your patient, there was a large number of radiopaque markers still retained, so there's evidence of delayed transit. And it also suggests that most of them are localized in the rectosigmoid area, suggesting that it could be dyssynergic defecation or functional rectosigmoid obstruction. If it's diffusely delayed colonic transit or colonic inertia, often these radiopaque markers remain distributed through the right transverse colon and also the left colon. Throughout the whole colon, actually, you have a nice outline of the colon in cases of markedly delayed colonic transit.
DR. SATISH RAO: Okay. So that's a very good point you made there. What I want to also bring up to the attention of our audience, really, is, you know, the traditional paradigm has been that, when you do a colonic transit study, you see this very compartmentalized result, where you have all markers held up in the rectum or rectosigmoid region or you have a diffuse distribution. Now that may well be true and, if you have it, it probably helps you a little bit, as Henry just said. The diffuse distribution suggesting slow transit and the rectosigmoid holdup suggesting more dyssynergia.
However, in repeated studies, both by our group and other groups, has shown that, in up to two-thirds of patients with dyssynergic defecation, there is, indeed, diffuse distribution of colonic transit markers. It makes physiological sense [that] if you do have an outlet obstruction, you're not going to poop and things will be slow or there is secondary slowing of colonic transit and that's something we should all be aware and not just dismiss that kind of a pattern as being highly indicative of slow transit alone without excluding dyssynergia. In other words, all of them, once you find slow distribution or excessive markers, you will need to do a pelvic floor evaluation to exclude dyssynergia before categorically diagnosing slow-transit constipation.
DR. HENRY PARKMAN: Satish, can I ask you a question? Is the converse true? If the colonic transit appears normal, a lot of physicians can do colonic transit, but they might not have access to anal manometry. If the colonic transit is normal, how does that impact on the diagnosis of functional dyssynergic defecation?
DR. SATISH RAO: I think at least a third of patients with dyssynergic defecation will have a normal colonic transit. So it is important not to base your diagnosis exclusively on colonic transit and that's because, what happens to these folks is they have repeated urges to go. They go up to eight times a day sometimes and multiple times they visit and eventually or they use physical maneuvers and digital maneuvers and suppositories to ultimately empty themselves. So that is how they manage to eventually clear the colon of stool.
So normal transit does not exclude dyssynergia. You will still have to depend on their symptoms and look at other criteria such as the manometric evidence for dyssynergia and/or balloon expulsion or defecography evidence to support dysergia.
DR. ANN OUYANG: I do think it's important to just point out that patients should not be on their laxatives when they do the transit studies. Because they can have a normal-appearing transit where the actual function of the colon is impaired.
DR. SATISH RAO: Yeah, that's an excellent point, Ann. In fact, I agree with you there. I, in fact, [have] most of my patients stop all laxatives, all prokinetic agents at least two days before they ingest their capsule and then for seven, up to six days, really, after that. So, yes, they are off all markers, all medications. That's very important.
So, as you can see, based on this X-ray, there is holdup suggesting slow transit, but, given the holdup more in the left side, it's more likely that there is -- dyssynergia is a possibility.
Let's look at this next panel and let me just describe this first and then maybe have Ann comment on how she would interpret this. So, here, we have a sample of this lady's anorectal manometry. There are four-channel pressure recording that you can see. The top panel shows the rectal pressure activity, the second, third and fourth panel show anal pressure activity at the outermost or rather, the lowermost line is the anal sensor at 1 cm from the anal margin. The second one above it is 2 cm and the one above it is at 3 cm from the anal margin. In other words, the lowermost one is external anal pressure activity and the upper two are more on the inner aspect of the anal sphincter activity.
And to the left is the baseline rectal activity or baseline anal and rectal pressure activity and then, later on, we have the patient attempt defecation, push or bear down and those are the changes that you're seeing there.
Also, what we did here was distended the balloon with 60 cc of air to give her a feeling as if there is some stool-like sensation. The second thing we did was we had her sit up on a commode to give her a much more natural feeling as if she had to defecate. So she is attempting defecation in this sitting position with an air-filled balloon in the rectum, giving her a feeling as if there is some stool there and we've asked her to attempt defecation.
So, Ann, can you take it away and tell us how you would interpret this?
DR. ANN OUYANG: Well, I think, usually, when people try and defecate, they should silence the pelvic floor, so there should be relaxation of the pelvic floor and that doesn't seem to be happening here, suggesting, then, she's unable to relax the pelvic floor appropriately.
DR. SATISH RAO: So what you can see from the rectal channel, there's a rise in intrarectal pressure, suggesting that she's generating good pushing effort, but she makes multiple attempts; it's not like one uniform effort. But all the anal channels, the pressure activity rises, which clearly suggests that she has paradoxical anal contraction or dyssynergic defecation.
So with this as a finding, the usual treatment approach would be to perform biofeedback treatment. That is now recognized as the best approach for this treatment. And here is the same patient, after four sessions of biofeedback, you can now see that she generates a good pushing effort with the rectal pressure channel rising and, simultaneously, you can see that there is nice coordinated relaxation of the anal canal, showing that she has now mastered the technique of coordinated relaxation of the pelvic floor, and let's see whether this also translates into other functional improvement, such as maybe a colonic transit study.
Let me have Henry comment on this post-biofeedback colonic transit study using the same method, three capsules, one X-ray at 120 hours.
DR. HENRY PARKMAN: Well, in this X-ray, I count about only four radiopaque markers and 72 were given, so after the five days, there's nearly complete evacuation of the markers. It seems like a very good analogy to the improved defecation you saw on the anal manometry that she's actually able to improve the transit through the colon.
And these are objective parameters. The main thing now is to actually ask the patient how she's doing. It seems like she's probably doing a lot better, but, Satish, how's the patient doing clinically after this?
DR. SATISH RAO: Well, clinically, she was reporting significant improvement in her symptoms. She does not have to strain much. She is having daily bowel movements and she was very, very satisfied. On her own satisfaction score, she was 18% over a scale of 0 to 100 at baseline and she was giving herself about 85% satisfaction with her bowel movement. And that, you can see, is reflected by improvement in the manometry and also by the colonic transit study.
Treatment Approach to Dyssynergic Defecation
I would like to just sum up the approach to dyssynergic defecation treatment. For years, we've been doing biofeedback treatment, but there has been some concern as to whether this is indeed efficacious or not, because we give these patients a lot of attention, we teach them coping strategies in life as well as the bowel habit and so on. And whether it is all the coping skills that we're giving them or the attention we're giving them is making the difference or is it truly the physiological conditioning that is indeed making the difference.
So, to sort this out, we have done a randomized controlled trial. There have been two other controlled trials, one from Bill Whitehead's group and another one from Italy, all coming to fairly similar conclusions. Let me share with you this data which is current was presented at DDW last year.
We have two panels here. On the left-hand panel, the data shows the changes in the mean complete spontaneous bowel movements per week in the pretreatment group. We had about eighty patients who were randomized to biofeedback treatment, to sham feedback treatment and to standard treatment with laxatives, diet and exercise alone. Now, as you can see, when compared to their baseline complete spontaneous bowel movement frequency, which was around 3 in the biofeedback group, it increased to nearly 6.5; there was significant difference. Whereas, in the other two groups, there was a small change, but this was not significantly different, showing that biofeedback was clearly a superior and more effective way of dealing with these patients' condition.
In the right-hand panel, what you can see is the presence of dyssynergia pattern. At baseline, of course, all three groups had dyssynergia, but only in the biofeedback group, there was an 84% improvement in the dyssynergia pattern, whereas, in the other two groups, the dyssynergia essentially persisted at the end of three months of treatment.
So I don't believe now that the time is right for us to entertain the diagnosis of dyssynergia in the usual algorithm of assessing patients with chronic constipation. And, if there is a suspicion, based on your clinical evaluation, proceed with appropriate diagnostic testing using both colonic transit study, anorectal manometry and a balloon expulsion test and sometimes defecography can -- if the manometry's not available, defecography can provide evidence for this.
And once you identify dyssynergia, I do believe that laxatives or prokinetics alone will not treat the patients in the long term; they will continue to suffer. The only effective way to treat them is through biofeedback treatment.
DR. HENRY PARKMAN: Satish, thanks a lot for that interesting case. If I can just follow up with one short question. Your case does illustrate the use of using anal manometry to diagnose dyssynergic defecation. Often, those are only available at certain centers. You've mentioned balloon expulsion. Is that something that other physicians could be using as a screening test for this disorder?
DR. SATISH RAO: Absolutely, Henry. I think balloon expulsion is a simple bedside test that can be done to evaluate the possibility of outlet dysfunction. And the simplest way to do this would be to tie a party balloon or a finger cuff from a glove onto a little plastic tube, insert that into the rectum, fill it with about 50 mL of water, have your subject sit on a commode, start a time clock, walk away, give them privacy for about five minutes and see if they can expel it.
Most normal individuals can expel a balloon in less than one minute. If it happens, then it's probably unlikely, however, I do know that many patients with dyssynergia can expel balloons, so it doesn't completely exclude it. But if they can't expel the balloon, I think that helps you in your clinical diagnosis of dyssynergia.
DR. HENRY PARKMAN: Satish, again, thank you, that was a very interesting case.
Presentation of Case 2
Let's continue our discussion by considering the case that Dr. Ann Ouyang is going to present. This is a case of a 47-year-old African-American woman presenting with nausea and vomiting.
DR. ANN OUYANG: Yes. I'm presenting a 47-year-old African-American woman. She presented with nausea and vomiting. At her initial presentation, the symptoms she complained of, this nausea and vomiting, had been present for about six months. The nausea was unrelated to eating, it was constant and she was vomiting every other day.
She had been evaluated prior to being sent to our institution. She'd had an upper GI and small-bowel followthrough and an endoscopy and a colonoscopy; all were normal. Her past medical history, she had had a tubal ligation, appendectomy, umbilical hernia repair and a tummy tuck in 1990. She was married; she had two children and there was a family history, mainly of hypertension.
DR. ANN OUYANG: Her current medications are metoclopramide, Protonix , Zofran and she's on a stool softener.
Her family and social history, she worked for a hospital billing company. She denied any alcohol intake and did not smoke cigarettes.
Her review of systems was fairly significant for a forty-pound weight loss, really because of anorexia secondary to her nausea. She did mention that she was constipated and she had no other significant complaints. Her current weight, on physical exam, was 156 pounds. Her blood pressure was fine. Her physical examination revealed normal head, ears, eyes, nose and throat. Normal cardiac and chest exam.
Her abdominal exam, she had some decreased bowel sounds. There was no succussion splash. She had no hepatosplenomegaly or masses. She had some mild tenderness to palpation in the lower abdomen.
Rectal examination revealed some brown stool. It was Hemoccult-negative and there was no apparent abnormality when she tried to strain.
I'd be interested in your consideration of the differential diagnosis at this time and what studies you might consider. Henry?
The Differential
DR. HENRY PARKMAN: Well, we have a lady who actually presents with a lot of upper symptoms, nausea and vomiting. And, because of that, she's reducing her appetite and losing weight. Interesting, then, in the review of systems, she also has marked constipation. And in my thinking, she has both evidence of upper and lower GI motility dysfunction and what I would be considering is something like a diffuse GI motility disorder such as chronic intestinal pseudoobstruction.
Could this be a functional bowel disorder? There are cases with irritable bowel syndrome, overlaps with functional dyspepsia so you can get both upper and lower symptoms, but her nausea and vomiting is quite excessive for these functional disorders, and I would think more towards gastroparesis. This is a type of patient with both evidence of upper and lower symptoms. And we might proceed with, at our institution, a whole gut transit test measuring both gastric emptying, small-bowel transit and colonic transit to find out where the most severe motility problem is and try to help direct the therapy.
DR. ANN OUYANG: Thank you. Satish, is there anything that you would add?
DR. SATISH RAO: Yeah, I think it's a very interesting case. A little complicated, as you rightly said. The main thing is this a structural dysfunction or is it a functional dysfunction? And I think, from your evaluation that you've received so far, structurally, most things seem to be intact. So we're really looking at a functional gastrointestinal disorder.
Then, as Henry pointed out, the question is, is it an upper gut dysfunction or a lower gut dysfunction or both? What I've seen very often is it is missed and overlooked is the lower gut dysfunction can lead to upper gut dysfunction. Probably this is a case of that.
In fact, it's been shown, experimentally, that if you can distend the rectum painlessly for prolonged periods of time, you can actually slow both gastric emptying and small-bowel transit. So this may be one of those situations where the patient may have a lot of constipation, but they don't really look at constipation as an issue, but because the nausea, vomiting is important, that's what they're presenting with as an important symptom.
The other quick thing is her nausea, vomiting seems to be unrelated to eating, which I think is also an important point. Because, often, in the gastroparetics or diabetics, for example, often, it seems to be related to eating.
DR. ANN OUYANG: Thank you. Well, that was, also, our initial thought was whether this was actually an upper functional bowel problem. And we did question whether she might have gastroparesis.
She had had other surgery. So the question whether the nausea could be secondary to some partial obstruction, she had had a small-bowel followthrough, making that unlikely to be significant. Also she was not complaining of a significant amount of pain.
Imaging, Lab Results and Functional Tests
So our next approach was to do abdominal X-ray and also an obstruction series and a gastric emptying. This slide shows the abdominal X-ray, which was fairly unremarkable; certainly there were no air-fluid levels. There is some stool there in the colon. She also underwent a gastric emptying and, Henry, do you want to comment on this?
DR. HENRY PARKMAN: Sure, sure, I'll be glad to. At our center, she would ingest a technetium-labeled egg sandwich and we'd do an image of the abdomen right after the meal ingestion, and we'd do it every thirty minutes out to at least two hours. At our center, we do it out to four hours, because that's a little better marker of gastroparesis.
In this particular patient, she had 58% emptying at 120 minutes, and that's normal. At the end of two hours or 120 minutes, you want to have at least 50% or half the meal emptied.
DR. ANN OUYANG: Thank you, Henry.
DR. SATISH RAO: Oh, can I just ask you, Henry, there, when would you think that the four-hour emptying is important?
DR. HENRY PARKMAN: Well, we did, actually, a study looking at that where, over one year, all our patients undergoing a gastric emptying test had the imaging out to four hours. We were able to pick up some additional patients with gastroparesis who had normal emptying at the end of two hours that were picked up when you followed the curve out for four hours. So, in this particular patient, it might be helpful if you did have an extended gastric emptying to four hours. At our practice, we routinely do this in everybody.
DR. SATISH RAO: So you're saying that, if a two-hour emptying is abnormal, then that's enough to stop the test, but, if it is normal, then maybe it may be worth going to four hours, because you'll pick up several other people.
DR. HENRY PARKMAN: Yes, exactly. Now, practically, it's hard to analyze a study at the end of two hours, usually wait to the end of the day. That's why at our center, we just get the study out to four hours on everybody getting the test. What you say is right, if it's abnormal at two hours, you don't have to continue it, because you've already had the diagnosis of gastroparesis. Her two-hour study was normal.
DR. ANN OUYANG: Okay, thank you. She did have some lab studies also, which did show a normal electrolytes, normal calcium and normal thyroid stimulating hormone. And I believe there was a report indicating that patients with hypothyroidism, many of them do have constipation. The yield of doing TSH in everyone with constipation is low for showing hypothyroidism, but that is one of the studies that we usually do. At this point, with the normal gastric emptying, what other assessments would you do at this time? Satish?
DR. SATISH RAO: Well I think it would appropriate to proceed with colonic evaluation in the form of colonic transit study with Sitzmarker perhaps, and also anorectal manometry and balloon expulsion test and perhaps defecography, along the lines we discussed earlier. Those would be useful tests, I think, in the further evaluation of this patient.
DR. ANN OUYANG: Thank you. Well, the abdominal X-ray had shown some retained fecal matter and, at this point, she was asked for more specific information about her bowel movements. And she admitted to bowel movements actually only once every seven to ten days. This had been a problem she'd had for many years, despite maintaining a high-fiber diet. And she did say that the constipation had become worse in the past six months.
At this point, she was started on a polyethylene glycol medication, MiraLax , as well as Fleet's phosphosoda enemas. And she did have improvement in frequency to moving her bowels every three days. Along with that, she did notice less vomiting, but she was having a significant amount of abdominal pain associated with the effect of MiraLax. Henry, would you agree with Satish's plan for further assessment and workup?
DR. HENRY PARKMAN: Yes. The only thing that I was entertaining is: Would an antral duodenal manometry be helpful in this particular patient? She had normal gastric emptying. I'm still struck by her symptoms, [which] are mainly nausea and vomiting, although you'd have nicely got out the marked colonic dysfunction with infrequent bowel movements, very rarely with antral duodenal manometry, can [you] pick up cases of occult partial small-bowel obstruction with upper symptoms. And this patient does have the history of the abdominal surgery. So that might be something, in a very tertiary-care center, you might want to do.
But I think, given the fact that she has infrequent bowel movements, looking at a colonic transit test would be helpful at this time.
DR. ANN OUYANG: Thank you, Henry. I think our feeling was that her nausea and vomiting improved sort of concomitant with the improvement in her constipation, so we did tend to focus on the constipation at this point. And our approach was to think about the possible cause of constipation here.
One would be an anatomic abnormality; she had a normal colonoscopy. Medications are a very common cause of constipation and I think it's very important to review all the medications the patient is taking, including potentially non-prescribed medicines and she was on nothing that we would expect to cause constipation. Metabolic causes, we did talk about briefly and she had normal chemistry.
So we felt that we were, at this point, looking at colonic inertia or outlet obstruction and we did proceed with a sitzmark transit study, an anorectal manometry and a defecogram in her case.
In terms of differentiating colonic inertia versus outlet obstruction, I think we discussed this in some depth in the case that Satish presented. And somewhat the evaluation, as we mentioned, depends on what techniques are available at each institution.
At our institution, the sitzmark transit study we use is similar to what Henry described, which is to take one capsule with the 24 markers and then take the X-ray at five days. We also have anorectal manometry capabilities and defecogram.
There are different ways of doing the anorectal manometry and the slide I'm showing here is a snapshot from this patient's anorectal manometry. We use a solid-state probe, so, at any time, we're actually recording just from one place and we're recording in the four different dimensions, anterior, posterior, left and right. And this tracing that we're showing is really of the response of the anorectal sphincter, the internal anal sphincter to balloon distension in the rectum. And what it does show is relaxation of the internal anal sphincter in response to balloon distension, therefore excluding short-segment Hirschsprung's disease, which, as we mentioned, similar to the last case, would be unusual in somebody who did not have it really from very early age.
I just want to mention the use of this anorectal manometry which can record in the four directions is probably even more helpful in patients with incontinence where you think there may be disruption of the anal sphincter, often secondary to childbirth, and that can tell you which orientation there is of decrease in pressure.
Satish, do you have any comments at this point?
DR. SATISH RAO: No, I think we are moving along nicely. I think that I would probably presume that after you have done your rectal anal manometry inhibitory reflex, you would ask this patient to attempt defecation and you would look at the manometric changes in the rectum and anal canal. And probably look for dysynergic patterns and that's what I would do. Can you tell us what you found at the attempt at defecation?
DR. ANN OUYANG: Yes, she had a normal response to straining and normal sensation.
DR. SATISH RAO: All right. So that would probably exclude pelvic floor dysfunction or dyssynergia, anyway, as a major contributor to her symptoms.
Tell us what happened with the colon transit study, then, please?
DR. ANN OUYANG: Right, the next slide is an abdominal X-ray, it's part of the Sitzmark transit study. On day zero, which is the day she was given the markers, you can see them all in the stomach. The next X-ray shows the abdominal X-ray from day five. And, on this X-ray, there are some scattered markers, mostly in the left upper quadrant and some in the transverse colon. There are no markers in the rectosigmoid. Henry, do you want to comment on that?
DR. HENRY PARKMAN: Yeah. Well, she has an increased number of markers in the colon; abnormal's more than six and I believe she has more than six.
DR. ANN OUYANG: Yes.
DR. HENRY PARKMAN: Okay. We talked before about trying to use the pattern to help differentiate colonic inertia versus rectosigmoid obstruction. The main purpose of the sitzmark test, though, is to measure transit of the colon; she has abnormal transit. It suggests it's not rectosigmoid obstruction as your anal manometry also suggests it's not. So it suggests she's got delayed colonic transit.
DR. ANN OUYANG: We did do a defecogram and I hope this will show up on the slide. The defecogram involves putting barium into the rectum and then having the patient strain and evacuate it. One usually measures the angle between the rectum and the anal canal and that angle should become more obtuse, should straighten out as there's relaxation of the pelvic floor and the patient then can evacuate the contrast.
And this defecogram shows normal emptying of the rectum. So this was another confirmation there was not holdup in the pelvic floor. So, at this point, what would you do next, Henry?
DR. HENRY PARKMAN: Well, her objective finding showed delayed colonic transit. She has significant constipation. She's had numerous therapies that have been unsuccessful. The one prokinetic [therapy] that might be useful for her would be tegaserod, a partial 5HT4 agonist, because she has upper symptoms but also marked colonic inertia. And had she been on that therapy?
Treatment Options
DR. ANN OUYANG: Well, we'll talk about what medications, but I would be interested in Satish's comment about whether a colonic motility study might be of use at all in this patient.
DR. SATISH RAO: Yeah, I think this is probably the right time to think about studies such as colonic manometry, although, as Henry just mentioned, I'd like to see patients who have probably tried some of the medications that are available, such as tegaserod. She clearly appears to have failed most general laxatives, so more prokinetic agents such as tegaserod or maybe lubiprostone is what I would be doing. And, assuming that the patient is not responding or has failed to respond or there is evidence that there are some other issues involved, then I think, at this stage, you're really looking at options such as removing the colon, perhaps, to mend her constipation.
Now, I believe that the technology has advanced sufficiently now that we should be moving away from the research realm into clinical realm of using ambulatory colonic manometry for defining the colonic motor function and perhaps even the sensory function. And also, to some extent, we can look at colocolonic reflexes in these people.
In a nutshell, you place a solid-state manometry probe, perhaps up to the hepatic flexure, and record colonic motility over 24 hours. And in studies done here and Europe, we have shown that patients with constipation may demonstrate either a normal colonic normal motor function or patterns suggestive of neuropathy. Primarily, we're looking at three important changes, presence of high-amplitude propagated contractions, whether they have a gastrocolonic response or not and, when they wake up, whether they have a normal waking response. If two out of three of these patterns are absent, then that will favor a colonic neuropathy. Or, if these patterns are present, but attenuated significantly, then that will favor a myopathy.
In our hands, we have seen that, if you have a neuropathic kind of a colon, those colons will not do very well with whatever you do in terms of treatment, the prokinetics or behavioral approaches, and they are best-served by having a colectomy. Whereas, if you have a normal pattern or a myopathic pattern, you can still assist them with more aggressive treatment with laxatives and behavioral therapy. So that is the rationale, if you like, for doing the ambulatory colonic manometry.
DR. ANN OUYANG: Well, that's very interesting. It sounds like it's close to becoming a very useful clinical tool.
In this patient, were tried a number of laxatives and medications in various combinations; they were unsuccessful. She did have a repeat transit study, which, again, confirmed slow transit. And she did undergo a subtotal colectomy with ileorectal anastomosis with very good outcome.
I'd just like for us to just review the medical treatment options and then mention the surgical. Now, and this patient had been tried already on a number of them. She was actually treated before lubiprostone became available, so that was not one of the options that she was treated with.
Just for our audience to go through some of the other approaches for patients with constipation. Bulking agents such as fiber are often used. May have the side effect of bloating. I just think there's no real good randomized study showing they're really helpful in really significant constipation, but I think it's a useful first step in people with minor constipation. Stool softeners such as mineral oil and docusate are often used and, again, for sort of mild complaints of constipation, can be helpful.
The osmotic laxatives, certainly, for people with more severe constipation, have been very helpful. The polyethylene glycol-based ones and as well as lactulose and magnesium hydroxide can also be used. Stimulant laxatives such as Ex-Lax and bisacodyl are a standby that many patients find helpful. And the more recent pharmacologic agents, tegaserod, a 5HT4 receptor agonist, and, most recently approved, lubiprostone, the chloride-channel opener. Satish, do you have any comments about your approach to using these various medical options?
DR. SATISH RAO: I think so. I really think that, now, you know, we know that laxatives are really generally useful for occasional constipation. We have tried them, because that's all we had, but now we have these nice, new agents which are more selective, which are neuromodulators and probably act in a much more physiological way, augmenting colonic function. For example, as you mentioned, Tegaserod is a 5HT4 agonist. It actually stimulates the 5HT4 receptor on the nerve terminal, brings about release of acetylcholine and CGRP and then acts on the muscle endplate and, thereby, induces peristaltic contractions. And you've also mentioned lubiprostone which is another new agent just approved which is a chloride channel secretogogue and that really has been shown to both accelerate transit in a recent study from the Mayo Clinic group and also we know that it increases stool frequency and consistency and bowel movement. So these are clearly the agents that are now coming into the armamentarium of gastroenterologists where we can really improve colonic motor function by using more selective physiologically-based treatments and I think that's what I would do first, I agree with you there.
DR. ANN OUYANG: Henry, do you have anything to add?
DR. HENRY PARKMAN: Well, I'm looking forward to the use of Amatiza or Lubiprostone. As Ann mentioned, it's a chloride channel opener and it increases fluid secretion into the GI tract, increases the water content going into the colon. It's actually able to significantly increase the number of bowel movements that these patients with chronic constipation have. So I'm looking forward, there's a new additional agent that we can use in some of these patients.
DR. ANN OUYANG: Yes. My approach is just a little bit different, I think, in considering cost. If a patient has a good response to really over-the-counter and the sort of standby medications, that's what I usually would try first. And if they don't have a very good response, then would move to more of the prescribed medications.
In terms of the surgical approach, there are reports of doing segmental resections or subtotal colectomies. I think the surgical literature is, you know, much more difficult to tease out, in some ways, because it's obviously hard to do randomized controlled trials.
Just looking through the surgical literature, I think the consensus would be that subtotal colectomy with ileorectal anastomosis is somewhat more successful than segmental resection. There are some reports that do recommend confirmation of slow transit before surgery, so you have more than one, because it is obviously a nonreversible approach.
And looking at outcomes, often, there's improvement in the frequency of bowel habits, but many patients will still have a quality of life that is worse than control subjects. So it's not a panacea that's going to make them feel completely better and I think that's important to discuss.
DR. HENRY PARKMAN: Well, can I add something, Ann? If you're going to consider a patient for surgery for chronic constipation, you have to be very careful to evaluate your patient's upper GI tract as well as the lower GI tract. The patients that do well with surgical treatment are those with isolated colonic inertia. If they have evidence of upper GI motility disorders such as gastroparesis, they often do very poorly with that sort of disorder.
Also, you mentioned that the anastomosis is an ileorectal anastomosis and that's good for this patient where you had an intact internal anal sphincter relaxation. But if they have evidence of impaired relaxation or also concomitant pelvic floor dyssynergy, then you might have the patients [undergo]an ileostomy with the surgery.
DR. ANN OUYANG: Yes. I mean, I would also say that even if you were to find colonic inertia, because, obviously, which you find first depends on which test you do first. If you do a transit study and you find they have colonic inertia, it's very important to make sure they don't have a concomitant pelvic floor dyssynergia, because overlap is fairly common. And our approach has been, if they have pelvic floor dyssynergia, then that has to be addressed before you would consider surgery. Satish, do you have anything to add to that?
DR. SATISH RAO: No, I think you guys have very nicely summarized most of the key issues here. I think we need to really make sure that the patient does not have dyssynergia. If so, that has to be treated first and, in spite of that, if the patient has significant symptoms, then to consider colectomy. As Henry nicely outlined, really upper small-bowel manometry evaluation is important.
There's only one other point I want to add and that is the literature tells us that, if in addition, if these folks have either significant abdominal pain as an important component or significant psychosocial issues or, particularly, the psychological issues, they should also be addressed, because, in one series, when they did surgical colectomy, 80% of those who did poorly after colectomy were those folks with surgery psychological dysfunction.
So I think it may be important to first assess for psychological dysfunction. If present, to treat that effectively and only then embark on surgical therapy and that is important; that should also be taken into consideration.
DR. ANN OUYANG: Right. And our next slide kinda summarizes that, which are the relative contraindications. One being significant psychological comorbidity, a history of laxative abuse and a diffuse motility disorder with upper intestinal motility disorder, as Henry pointed out.
So I think that the teaching points that we certainly had from this case was that upper GI symptoms can originate from parts of the bowel which are not in the upper GI tract and that it is very important to get a very complete history and a review of symptoms.
We hope we reviewed the differential diagnosis of constipation in this case and Satish's case. I think both of them really indicated that it's very important that these patients be evaluated with the pathophysiology in mind and potential treatment options as an algorithm of approaching patients. And then to just mention, as we did, the surgical options for patients with constipation with the indications and contraindications.
Conclusion
DR. HENRY PARKMAN: Well, thank you, Ann, for that very interesting case. And also Satish for your case, it was very informative. One case of functional rectosigmoid obstruction or pelvic floor dyssynergy and this patient here of colonic inertia that it actually was so severe that it presented with upper GI symptoms.
Satish and Ann, I was wondering, as we're getting ready to close up, if you had some important pearls that you'd like to offer to our gastroenterologists that are watching about managing patients with conditions such as chronic idiopathic constipation. Ann?
DR. ANN OUYANG: Well, I think it's very interesting that there is a pathophysiologic basis for constipation. It's a fairly logical approach. I think that being able to differentiate a diffuse motility disorder, an anatomic problem, the colonic inertia and pelvic floor dyssynergia give a framework in which to approach these patients, a framework in which to do the studies and a rationale behind some of the treatment options that we choose. So I think it makes it a much more logical condition to really approach and treat. Satish?
DR. SATISH RAO: Yes, Ann and Henry. I think the first thing is to say is we have really come a long way in our approach to managing constipation. It is a heterogenous condition, as we have outlined just now with the two cases with multiple symptoms.
The second thing we have learned is symptoms alone do not predict the pathophysiology. And, clearly, in the absence of secondary causes, one should take a pathophysiological approach and do the diagnostic tests that we have outlined. And with the diagnostic tests, it will give you nice potential treatment opportunities, such as, in the presence of dyssynergia, you can use biofeedback or, in the presence of slow transit or normal transit functional constipation, you have other approaches that you can try.
What I'm really excited about in this field today is we now can use a pathophysiological-based treatment approach. You know, if you have functional constipation, you can probably use tegaserod or lubiprostone. Slow-transit constipation, you can use the same. If you have upper and lower symptoms, as in the case that Dr. Ouyang presented, we can, again, consider tegaserod because there's effects on the upper and lower gut. And if the symptoms are predominantly dyssynergia, I think you can go towards biofeedback.
So we have a number of therapeutic armamentarium that are available, provided we understand what is causing the patient's symptoms and problem, and then use these methods or treatment modalities to help our patients. And we have several more compounds coming in the pipeline such as alvimopan, which is a mu-opioid antagonist and other compounds which I think will increase our ability to treat these patients using medical means.
DR. HENRY PARKMAN: Thank you, Satish. I think these two cases illustrate the evolving field of neurogastroenterology that encompasses both GI motility disorders as well as functional bowel disorders. Here we've had patients with chronic constipation. One had chronic constipation from functional rectosigmoid obstruction; one had symptoms from colonic inertia. With the field of neurogastroenterology, as Satish and Ann mentioned, by understanding the pathophysiology and possibly the reason for the patient's symptoms, you can help direct them to a more appropriate therapy and they -- hopefully, a better patient outcome.
At this time, I would like to thank both Ann and Satish for joining me in this discussion of this interesting topic of chronic constipation I would also like to thank the audience as well for , and joining in this discussion. Thank you. I'm Dr. Henry Parkman from Temple University.
DR. SATISH RAO: Thank you, Henry.
DR. ANN OUYANG: Thank you.
