Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome
Condition: Lynch Syndrome; Small Bowel Neoplasia
MeSH terms: Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Syndrome
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary
      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. This is a national multi-centre study
      evaluating the yield of small bowel screening using capsule endoscopy (CE) and double balloon
      enteroscopy (DBE) 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. The 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.
    

Detailed description: 
      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.
    

Intervention name(s): Capsule endoscopy
Intervention type(s): Procedure
Intervention description(s): Capsule endoscopy at baseline and after 2 years
Other intervention name(s): Capsule endoscopy PillCamSB
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Lynch syndrome; HNPCC; Capsule endoscopy; Small bowel cancer; Double balloon endoscopy