Small bowel surveillance in patients with Peutz-Jeghers syndrome: comparing MR enteroclysis with double balloon enteroscopy.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder,
characterized by gastrointestinal hamartomas and mucocutaneous pigmentations.
The incidence is low and has been estimated to be between 1:8,300 and 1:200,000
births. PJS is caused by germline mutations in the LKB1 gene. The predominant
clinical features of PJS are the result of gastrointestinal polyposis, mainly
of the small bowel, which can lead to abdominal pain, bleeding and
intussusception already at a young age. The cumulative lifetime risk of
intussusceptions is estimated to be 70%, and half of all patients have had an
intussusception at the age of 20 years. Furthermore, PJS is recognized as a
cancer predisposition syndrome. Patients carry a high risk for the development
of both gastrointestinal and extra-intestinal malignancies. The relative risk
of developing any cancer lies between 10 and 18. For these reasons, PJS
patients are offered surveillance Surveillance of the small bowel is mainly
initiated to prevent complications (intussusceptions and bleeding) of small
bowel polyps and the starting age is young. Furthermore, small bowel
surveillance may prevent small bowel cancer or detect cancer at an earlier
stage. Although several new techniques have been developed for the
visualization of the small bowel, the optimal small bowel surveillance strategy
for PJS has not been determined, since no controlled trials have been published
on the best method and effectiveness.

The aim of this prospective study is 1) to evaluate the diagnostic efficacy of
DBE in comparison to MRE as surveillance technique of the small-bowel in PJS
patients, 2) to analyze patient burden and quality of life with DBE and MRE,
and 3) to evaluate the cost-effectiveness of DBE and MRE.

All patients with Peutz-Jeghers syndrome who are under surveillance at the
Erasmus Medical Center in Rotterdam or the Academical Medical Center in
Amsterdam, the Netherlands, are eligible for inclusion in this study. Included
patients will undergo an MRE, followed by DBE via the oral route. The physician
performing the DBE will be blinded for the MRE results. Number, location and
size of polyps will be correlated. Polyps >= 15 mm encountered during DBE will
be excised and analyzed histologically by a pathologist with gastrointestinal
expertise. Furthermore, biopsies will be taken of lesions suspect for
malignancy, as well as two biopsies of normal small intestine (duodenum,
jejunum and if possible ileum). If a polyp >= 15 mm is seen with MRE, but is not
detected during DBE, a new MRE will be performed one year after the first MRE,
to confirm or exclude the presence of this polyp.
Using questionnaires before and after the inverstigations, quality of life and
patient burden with the two different methods will be investigated.

MR enteroclysis (MRE) uses magnetic resonance imaging (MRI), without the use of
radiation, and enteroclysis. Contrast medium is infused in the intestine via a
naso-enteric tube by which maximal luminal distension can be achieved to detect
small bowel lesions. Double balloon endoscopy (DBE) is a new endoscopic
technique. With the use of two balloons attached on the tip and distal end of
the endoscope, the entire small bowel can be visualized. Furthermore, DBE can
be used for therapeutic interventions during the same procedure, such as
polypectomy.

All included patients will undergo an MRE as well as a DBE. Both techniques are
clinical practice for small bowel imaging and DBE is an adequate tool for
polypectomy. Accurate documentation of small bowel polyps in Peutz-Jeghers
patients and removal of large polyps can prevent complications of these polyps.
To avoid deprivation of adequate treatment for participating patients,
segmental unblinding of MRE results will be performed per small bowel segment
during DBE.
During the study, patients will not be exposed to risks other than the known
risks of MRE and DBE. Maximal three hospital visits are required for
participating patients, including one visit to the Erasmus MC for DBE. Each
investigation will take place in the outpatient clinic and will take 2 hours.
Furthermore, patients are asked to fill out 4 questionnaires during the study
period which will take approximately 15 minutes per questionnaire.