Trial Information

Chromoendoscopy in Lynch Syndrome Patients

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.