Capsule Endoscopy in Lynch Syndrome for Small Intestinal Tumor Screening
Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal
dominantly inherited disorder characterized by a very high risk of early-onset colorectal
and endometrial cancer and an increased risk of other cancers, including cancers of the
stomach, ovary, urinary tract, hepatobiliary tract, pancreas and small bowel. LS is caused
by germline mutations in one of the mismatch repair (MMR) genes, mostly hMLH1, hMSH2 and
hMSH6. Recently, several studies, including one from the Netherlands, have evaluated the
life-time risk of small bowel cancer (SBC) in LS patients. From these studies the life-time
risk of SBC is estimated around 4%. This is similar to the life-time risk of colorectal
cancer in the general population, for which screening is generally advised. The risk of SBC
increases with age, with an estimated prevalence of 1:500 at the age of 40, rising to an
estimated prevalence of around 1:70 at the age of 60. Compared with the general population,
LS patients with SBC generally present 10-20 years earlier as most patients with sporadic
SBC are in their sixth or seventh decade of life. The localisation of SBC in LS is almost
equal in the duodenum and jejunum, with localisation in the ileum generally occurring at a
lower frequency.Until now, screening for small bowel neoplasia in Lynch syndrome patients is
generally not recommended. However, the development of two new techniques to visualize the
small intestine has raised the question whether screening might be useful and advisable.
Small bowel capsule endoscopy (CE) has been developed as a safe, patient-friendly, minimally
invasive modality for visualization of the small bowel. In addition, double-balloon
enteroscopy (DBE) has been developed, a technique which allows endotherapeutic
interventions. The diagnostic yields of both techniques are markedly higher than the
conventional methods, such as push-enteroscopy and enteroclysis. To date, no study has been
performed on screening for small bowel neoplasia in Lynch syndrome patients by means of
these techniques.
The primary aim of the study is to determine the prevalence and incidence of small bowel
neoplasia in Lynch syndrome patients using small bowel CE and DBE.
Secondary objectives:
The secondary aim is to identify risk factors for small bowel pathology useful in clinical
practice to identify patients that might benefit from screening and to determine the
additional interventional risk associated with the endoscopic procedures.
This is a national multi-centre study evaluating the yield of small bowel screening using
capsule endoscopy and double balloon enteroscopy in Lynch syndrome subjects. The
intervention consists of performing a capsule endoscopy procedure at baseline and at 2-year
follow-up. In patients with polyps or malignant appearing abnormalities on capsule
endoscopy, double balloon enteroscopy will be performed with subsequent endoscopic or
surgical removal of neoplastic lesions.
Interventional
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Screening
The main outcome measure will be the number of neoplastic small bowel lesions, with determination of size, location and histological characteristics at baseline and at follow-up after 2 years.
At baseline and at 2 years
No
Jan J Koornstra, MD PhD
Principal Investigator
University Medical Centre Groningen
Netherlands: Medical Ethics Review Committee (METC)
CELSIUS
NCT00898768
May 2009
May 2013
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