Colitis, Ulcerative Clinical Trial
Official title:
Pelvic Collections on MRI in Patients With Ileal Pouches, and a Feasibility Study of Dynamic MRI Enema and Defaecating MRI Pouchography
A study to investigate the prevalence of pelvic collections in a representative sample of participants with normally functioning ileal pouches. It also aims to establish the feasibility and reporting variables for dynamic MRI enemas in ileal pouches and defaecating enema pouchography.
Ulcerative Colitis Ulcerative Colitis (UC) is the most common of the inflammatory bowel
diseases, with approximately 146,000 sufferers in the UK (NICE, 2011). Unlike other
inflammatory bowel diseases, the inflammation in UC affects only the large bowel, starting at
the rectum and extending proximally (towards the mouth end of the gut). Three in four
patients are managed with medical treatments with acceptable control of their disease, but
patients may require surgical removal of their large bowel for several reasons. The one in
four patients who have their colon removed (colectomy) either need an emergency operation for
infection, perforation or bleeding, or a planned operation for failure of medical management,
intolerance to medication, cancer or steroid dependence (1). Because the inflammation is
confined only to the colon, this surgery is curative.
Having removed the large bowel, there are options with regard to what to do with the end of
the remaining small bowel, the ileum. In 1978 Professor Sir Alan Parks and Professor John
Nicholls publicised their operation for 'restorative proctocolectomy' (RPC) folding and
suturing together loops of small bowel to create a 'pouch' to take over the reservoir
function of the rectum, and giving the patient the chance of continence without the need for
a stoma (2,3). This operation has become extremely popular over the last 38 years, and is
considered internationally to be the gold standard for 'restorative proctocolectomy' in
patients who choose not to have a permanent stoma (4).
The operation has been refined in the years since it's introduction (5), with roughly two
thirds of patients enjoying acceptable function. However, the complications associated with
creating an RPC; notably pelvic sepsis, fistulae, poor mechanical function and inflammation,
mean that the cumulative rate of pouch failure is roughly 5% at five years, and up to 15% at
15 years (Ryoo et al. 2014; Remzi et al. 2015; Sherman et al. 2014; R. et al. 2012;
Papadopoulos et al. 2010).
Pouch-Related Septic Complications St Mark's Hospital has one of the largest UK cohorts of
patients with RPCs, and is a tertiary referral centre for pouch complications. Of the reasons
for pouch failure, chronic pelvic sepsis is the major cause, at 50 to 60%. This is a long
term infection in the pelvis around or near the pouch, causing inflammation and poor
function.
The pouch itself may become inflamed, known as pouchitis, and the cause for this is unknown,
but it is hypothesised that the inflammation is caused by a change in the type of bacteria
present in the pouch as opposed to the small bowel when it was in normal continuity.
Generally speaking, the management of pelvic sepsis causing pouch function is to surgically
or radiologically drain the pelvic collection, or eventually surgically remove the pouch. The
management of pouchitis (primary idiopathic pouchitis) is primarily with antibiotics, but in
prolonged cases where antibiotics have been ineffective it may be in the patient's benefit to
treat the inflammation with steroids or 'biologic' medications. These medications act by
suppressing the body's innate immune response, and it would be inappropriate to use these
medications if the true cause of inflammation is ongoing sepsis in the pelvis because this
infection would likely become significantly worse, causing systemic infection (sepsis).
Unpublished research from St Mark's completed at the end of 2015
http://scripties.umcg.eldoc.ub.rug.nl/root/geneeskunde/2016/PloegVvander/ showed that in 68
patients treated for primary idiopathic pouchitis, 38% had an incidental pre-sacral
collection identified on MRI, potentially consistent with pelvic sepsis driving the
inflammation, rather than the inflammation rising primarily from the pouch itself.
Five patients went on to have drainage of the pelvic sepsis, with resolution of symptoms in
only one. Therefore, based on this series, the significance of a pre-sacral collection on MRI
in the context of pouchitis is unknown. Beyond this, it is not known how often this finding
may be present as a 'normal variant' in patients with normal functioning pouches. The
proposed trial would help to guide clinical management of patients with pouchitis and
pre-sacral collections.
Pouch Evacuatory Dysfunction
A different type of problem with ileal pouches is the inability to easily evacuate the pouch.
The majority of patients with normally functioning pouches, pressure to open their bowels is
felt just like people with normal anatomy. Some patients have difficulty evacuating the
pouch, often without an obvious inflammatory or anatomical cause. These patients are often
investigated with defaecating pouchography, which is an investigation using moving x-ray
images of radio-opaque contrast material being evacuated by the patient. A study conducted at
St Mark's and published in August 2016 (11) demonstrated that this investigation has a
relatively poor diagnostic value, partly due to the fact that there is no established range
of normal findings. Using moving MRI images in patients with normal anatomy (called MRI
defaecating proctography) is replacing the use of x-ray moving images (fluoroscopy) as there
is as much, if not greater detail on the images, and there is no radiation exposure for the
patient.
This study would be a pilot trial of the use of defaecating MRI in patients with pouches,
(defaecating MRI pouchography) to establish whether the technique translates to patients with
pouches instead of a rectum, and to establish what the range of normal findings are before
going on to utilise the technique in patients with evacuatory dysfunction. This technique has
not yet been described in the medical literature.
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