In determining the effect of a treatment for ulcerative colitis (UC), an ultrasound is not inferior to an endoscopy, according to a study in which patients were examined simultaneously with both methods.1 The study by Amsterdam researchers suggests that the use of ultrasound may offer an important advantage, because it allows several layers of the intestinal wall to be viewed, says researcher Floris de Voogd (Amsterdam UMC).
Significantly less burdensome for patients compared to an endoscopy and cheaper and faster to determine disease activity in UC: ultrasound has the potential to have important advantages for monitoring disease activity in UC. But relatively little research has been done into this way of examining the intestinal wall, says Floris de Voogd. “The studies into this have mainly looked retrospectively. In addition, these are all cross-sectional studies. Our study is the first study to follow patients over time and compare it to an endoscopy as the gold standard.”
The study enrolled 30 consecutive patients with moderate to severe UC (endoscopic Mayo score 2). All started on tofacitinib and were evaluated at baseline and after 8 weeks of treatment. At both time points, the bowel was assessed by both ultrasound and endoscopy. Subsequently, it was investigated whether the intestinal wall thickness measured with the ultrasound was associated with the response seen with the endoscopy. Endoscopic remission was defined as EMS = 0, improvement as EMS ≤ 1, and response as a decrease in EMS by ≥ 1.
The researchers found a good correlation between the findings with ultrasound and with endoscopy. De Voogd: “The intestinal wall thickness and the Doppler, which we can use to measure blood flow, are the two most important measures we used. We related this to the degree of endoscopic improvement. It turned out that the intestinal wall thickness is the most relevant parameter. In most cases, that is enough to determine whether or not someone responds to the treatment.”
Less intensive
An important implication of the findings is that it seems possible to prosecute UC patients with a considerably less burdensome and easier to use research method. This makes it possible to monitor the disease more intensively, emphasizes De Voogd. “In the treatment of IBD, it is important to act quickly to limit damage to the gut. The aim is to keep the disease in tight remission. Ultrasounds offer a particular advantage, because we can very quickly check whether or not there is inflammation in patients with minor complaints or a minimally elevated calprotectin. That can be done within a week and we can hardly ever achieve that with endoscopy. Usually an endoscopy means months of waiting because it involves a lot of preparation, while an ultrasound takes very little time. That is where the real benefit of using ultrasound lies.” The method is now widely used in the Amsterdam UMC and doctors are trained here in its use (see box).
Submucosa
In addition, it is possible with ultrasound to examine multiple layers of the intestinal wall. As a result, the technique may have an advantage over endoscopy, which only allows inspection of the mucous layer. And the new research may suggest that abnormalities in the submucosal layer are most relevant in UC. De Voogd: “We saw that the submucosa was the thickest in patients with inflammation, i.e. everyone in the beginning. The submucosa contains most of the blood vessels, so we think that it is mainly fluid that leaks from those vessels. Our hypothesis is now that disease activity is most prominent in the submucosa.”
There are also other research results that point to this, says De Voogd. “Another study looked at 89 patients who had their colon removed and also found that most of the disease activity occurs in the submucosa rather than the mucosa. That also makes sense: because the blood vessels are there, swelling can occur there. We are now investigating this in patients who have to undergo colorectal surgery. They receive an ultrasound beforehand and then we look under the microscope to see which layer is the thickest. If this confirms the previous findings, it could mean that UC is not so much a disease of the mucosa, as is now thought, but a disease that goes deeper into the intestinal wall. That’s an important difference with Crohn’s disease that cuts through all layers. But that difference may in reality be slightly less than we currently think.”
From this point of view, an ultrasound may have an advantage over an endoscopy. De Voogd: “In some UC patients we see a completely normal intestine during an endoscopy, but biopsies show that there is still a inflammation is. These patients also have a worse outcome in the longer term than patients who also have a normal intestinal wall at a microscopic level. As a result, it is currently recommended to take a biopsy regularly. But you can’t take a biopsy from the submucosa. So ultrasound might give us more insight into the disease than we currently have with just an endoscopy and possibly biopsies.”
Studie met calprotectine
For example, there seems to be an important role for ultrasound in the near future in monitoring the disease. De Voogd: “A combination of methods probably works best. Are most attractive than ultrasound and fecal calprotectin, because both are not very burdensome. It is difficult to say anything about the rectum with abdominal ultrasound of the intestines, because it is located deep in the pelvis. A combination of ultrasound with, for example, fecal calprotectin and symptoms could perhaps lead to fewer endoscopic procedures to determine disease activity in the future. We have therefore recently started a new study to see if we can get by with ultrasound and a stool sample.”
The researchers are also working on a score with which the findings can be quantified with ultrasound. De Voogd: “We want to develop a validated scoring system in which, for example, the thickness of the intestinal wall partly determines whether a patient should start treatment, and which indicates in which patients the disease activity has decreased to such an extent that the ulcers have disappeared. That’s what we’re working on right now.”
More than 1000 ultrasounds per year
The Amsterdam UMC has had experience with ultrasound for IBD care since 2016. This has since become standard care, says De Voogd. “We have been doing this on a large scale for at least 5 years and now make more than 1000 ultrasounds per year. We also have people who come here all the time to become proficient in technology. You also see that more and more hospitals are using this. With more and more young gastroenterologists trained at the Amsterdam UMC, this is spreading further across the Netherlands and I think that is a good development.”
References:
- De Voogd F, Van Wassenaer EA, Mookhoek A, et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022;163:1569-81.
- Gordon IO, Agrawal N, Willis E, et al. Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation. Aliment Pharmacol Ther. 2018;47:922-39.