A new ultrasonographic scoring model for stricturing complications in Crohn*s Disease: elastography, contrast-enhanced and small intestinal contrast ultrasonography combined

In the course of Crohn*s disease (CD) stricturing is a regular occurring
phenomenon. In 20% of patients strictures develop within 10 years of disease
onset with half of these patients facing surgery. Both inflammation and
fibrosis contribute to development of strictures in CD. However, where
strictures of mainly fibrotic origin are considered as end-stage of disease and
surgery is often inevitable, inflammatory strictures might be well treated
medically. Therefore it is of major importance to differentiate between
inflammatory and fibrotic strictures and adapt treatment accordingly.
Currently strictures are often diagnosed at endoscopy or by magnetic resonance
enterography (MRE) and subsequent treatment is often based on clinical and
biochemical disease pattern. According to previous studies, ultrasound
correlates with endoscopy, magnetic resonance imaging (MRI) and computed
tomography (CT) in disease assessment of CD. Furthermore, ultrasound might be
promising in monitoring stricturing disease. Several ultrasonographic
modalities, such as contrast-enhanced ultrasound (CEUS), elastography and small
intestine contrast ultrasonography (SICUS) have been developed and investigated
and are promising in diagnosing and characterizing strictures. A combination of
these modalities might improve assessment of strictures. Therefore we postulate
that the combination of several ultrasonographic modalities will reflect
strictures in CD and consequently of additive value in the assessment of
stricturing CD.

The primary objective of this study is to investigate if shear-wave
elastography and contrast-enhanced ultrasonography can identify those patients
most suitable fir an intervention (surgery or endoscopic balloon dilation) and
those patients that should receive anti-inflammatory treatment. SWE and CEUS
data of the stricture(s) in the group that do not receive an intervention
within one year will be compared with SWE and CEUS data of the intervention
group.

* What ultrasonographic parameters could be used to identify patients most
suitable for an intervention and what patients might benefit most from
anti-inflammatory medical treatment?
* Do CEUS and elastography correlate with each other?
* Comparing histology of resection specimen after surgery with ultrasonographic
data prior to surgery
* Development of a stricture scoring tool using ultrasonographic variables

Single-center, cross-sectional observational study

When stricturing disease is diagnosed patients will be discussed in a
multidisciplinary meeting and subsequent treatment will be planned. After
signed informed consent patients will be included. Clinical disease activity
scores and biochemical parameters will be collected. Furthermore, an intestinal
ultrasonography is planned. At the day of ultrasonographic analysis the
participant is asked to fast for six hours prior to the ingestion of oral
contrast. Then SICUS is performed and will take between one and two hours.
Subsequently, intravascular contrast is injected and CEUS is performed on the
region of interest (ROI), which will be the stricture(s). Then SWE is performed
on the earlier identified stricture(s). The combined procedure will take
between one and two hours in total.

The group of patients allocated to medical treatment will be followed for 52
weeks. After 12 and 26 weeks clinical disease activity scores and biochemical
parameters will be collected. When patients do not undergo surgery within the
52 weeks of follow-up clinical disease activity scores and biochemical
parameters will be measured and collected. Furthermore, a B-mode
ultrasonographic exam will be iterated at week 26 and 52. No surgery within 52
weeks will be classified as successful medical treatment.

All patients receiving endoscopic balloon dilation or surgery within 52 weeks
of baseline ultrasonography will be in the intervention group. In case of
surgery, if the previous ultrasonographic examination is older than 8 weeks
patients will receive a new ultrasonographic examination. In case of resection,
the resection specimen is collected and will be transferred to the pathologist.

The pathologist will secure the specimen, identify the stricture and its
length. Then, the specimen is prepared macroscopically following a local
protocol. At last, the specimen will be stored by the pathologist.
Subsequently, an IBD-experienced pathologist (AM) will assess the specimens
histologically on mainly inflammatory-predominant and fibrosis-predominant
features. Intervention within 52 weeks of baseline is another endpoint of this
protocol.

This study is not involved with major risks. For intravascular contrast the
most serious risk is anaphylaxis, although reported in less than 1:10.000
patients. Other minor side-effects, such as headache and nausea, are reported
in a small number of patients. For oral contrast no major or minor side-effects
are reported. However, diarrhoea could be a plausible side-effect and will
therefore be monitored. Other ultrasonographic modalities do not come with
notable risks.