Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome

NCT ID: NCT00905710

Last Updated: 2016-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2016-05-31

Brief 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.

Conditions

Lynch Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Conventional colonoscopy

Group Type: NO_INTERVENTION

No interventions assigned to this group

2

Colonoscopy using chromoendoscopy

Group Type: EXPERIMENTAL

Chromoendoscopy

Intervention Type: PROCEDURE

Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine

Interventions

Chromoendoscopy

Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• proven carrier of a MLH1, MSH2 or MSH6 mutation
• age between 20 and 70 years
• written informed consent

Exclusion Criteria

• previous large bowel surgery
• psychological/physical conditions hampering compliance with the study protocol

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Free University Medical Center

OTHER

Sponsor Role: collaborator

University Medical Center Nijmegen

OTHER

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Jan J Koornstra

dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan J Koornstra, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen, netherlands

Jan H Kleibeuker, MD PhD

Role: STUDY_DIRECTOR

University Medical Center Groningen, Netherlands

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

Stoffel EM, Turgeon DK, Stockwell DH, Normolle DP, Tuck MK, Marcon NE, Baron JA, Bresalier RS, Arber N, Ruffin MT, Syngal S, Brenner DE; Great Lakes New England Clinical Epidemiology and Validation Center of the Early Detection Research Network. Chromoendoscopy detects more adenomas than colonoscopy using intensive inspection without dye spraying. Cancer Prev Res (Phila). 2008 Dec;1(7):507-13. doi: 10.1158/1940-6207.CAPR-08-0096.

Reference Type: BACKGROUND

PMID: 19139000 (View on PubMed)

Huneburg R, Lammert F, Rabe C, Rahner N, Kahl P, Buttner R, Propping P, Sauerbruch T, Lamberti C. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening. Endoscopy. 2009 Apr;41(4):316-22. doi: 10.1055/s-0028-1119628. Epub 2009 Apr 1.

Reference Type: BACKGROUND

PMID: 19340735 (View on PubMed)

Haanstra JF, Dekker E, Cats A, Nagengast FM, Hardwick JC, Vanhoutvin SA, de Vos Tot Nederveen Cappel WH, Vasen HF, Kleibeuker JH, Koornstra JJ. Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial. Gastrointest Endosc. 2019 Oct;90(4):624-632. doi: 10.1016/j.gie.2019.04.227. Epub 2019 Apr 24.

Reference Type: DERIVED

PMID: 31028782 (View on PubMed)

Other Identifiers

ChromoLynch

Identifier Type: -

Identifier Source: org_study_id