Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome
Condition: Lynch Syndrome
MeSH terms: Colorectal Neoplasms, Hereditary Nonpolyposis; Syndrome
Study type: Interventional

Summary: 
      Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary
      disorder predisposing for colorectal cancer. To reduce the risk of colorectal cancer,
      patients undergo colonoscopy every 1-2 years. Chromoendoscopy is relatively new technique
      which improves the detection of adenomas, the precursor lesions of colorectal cancer. The aim
      of this study is to determine whether chromoendoscopy, including polypectomy of all detected
      lesions, reduces the development of colorectal neoplasia and the need for colectomy in LS
      patients.
    

Detailed description: 
      Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomally
      dominantly inherited disorder that accounts for 1-2 % of colorectal cancer cases. LS is
      caused by germline genomic alterations in one of the mismatch repair (MMR) genes hMLH1,
      hMSH2, hMSH6 and hPMS2. The lifetime incidence of colorectal cancer is 20-75 % in these
      mutation carriers. Individuals with LS-associated colorectal cancer differ from those with
      sporadic disease in several ways: the tumours are diagnosed at an earlier age; the majority
      of tumours is located in the proximal colon; there is an increased risk of developing
      synchronous or metachronous colorectal cancers and the prognosis relatively favourable
      compared to sporadic cases. It is generally accepted that LS associated colorectal cancers
      develop along the adenoma-carcinoma sequence as in sporadic cases. There is evidence
      suggesting that the adenoma-carcinoma sequence is accelerated in LS patients as compared to
      the general population.

      Colonoscopic screening and subsequent removal of polyps at a 3-year interval in asymptomatic
      at-risk members of LS families has shown to reduce the incidence of colorectal cancer and
      improve overall survival. However, within such an interval in surveillance programs, interval
      cancers have been observed. It is therefore currently recommended that MMR gene mutation
      carriers should be kept under surveillance by regular colonoscopy every 1-2 years beginning
      at the age of 20-25 or 5-10 years younger than the earliest affected family member.

      LS adenomas are predominantly located in the proximal colon and frequently carry villous
      architecture and high-grade dysplasia, markers that are associated with an increased risk of
      developing colorectal cancer. Even in LS adenomas smaller than 5-7 mm in size, high-grade
      dysplasia can be encountered. Therefore, the identification of high-risk precursor lesions in
      LS is considered of paramount importance.

      It is known that conventional colonoscopy has a certain miss rate for colorectal neoplasms,
      especially small adenomas. A few years ago, the technique of chromoendoscopy was introduced.
      Chromoendoscopy, in which one of various dyes are sprayed onto the colonic mucosa via a spray
      catheter passed through the working channel of the endoscope, offers detailed evaluation of
      the mucosal surface. Indigo carmine is a contrast stain that is not absorbed and does not
      react with the surface mucosa. In 2 large randomised controlled trials chromoendoscopy
      significantly increased the detection of small adenomas in the proximal colon as compared to
      conventional colonoscopy. Recently, 2 trials in LS patients revealed that chromoscopic
      endoscopy improved the detection of adenomas, particularly flat lesions, compared to
      conventional colonoscopy. Together, these data suggest that chromoendoscopy may improve
      detection rates of significant neoplastic colonic lesions in LS patients. However, the true
      value of chromoendoscopy in the management of LS patients remains to be demonstrated.

      The aim of this study is to determine whether chromoendoscopy, including polypectomy of all
      detected lesions, reduces the development of colorectal neoplasia and the need for colectomy
      in LS patients at follow-up endoscopy.

      The results of the study will indicate the value of chromoendoscopy in the management of LS
      patients and whether the technique should be implemented in current surveillance procedures.
    

Intervention name(s): Chromoendoscopy
Intervention type(s): Procedure
Intervention description(s): Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: colorectal adenomas; colorectal cancer; Lynch syndrome; chromoendoscopy