Observational study;
Confocal endomicroscopy in the diagnosis of colorectal neoplasia.

Rationale:

Colonoscopic surveillace is mandatory in patients at high-risk for colorectal cancer. However some practical issues makes this difficult (e.g. high frequency follow-up, high rate of flat adenomas - a notorious source of interval cancer - , and unnecessary removal of non-neoplastic lesions). Imperative to these data is to improve the accuracy of colonoscopic procedures. The role of confocal endomicroscopy in surveillance of patients at high-risk for CRC has been recently explored. It is presently not clear whether this technique has incremental benefit when added to traditional colonoscopic techniques.
Objective:

Two issues will be addressed:

1. does pan-colonic chromoendoscopy improve the diagnostic yield of colonic polyps (and in particular flat lesions) as compared to conventional colonoscopy?;

2. does pan-colonic chomoendoscopy combined with confocal endomicroscopy result in higher diagnostic accuracy of colonic lesions as compared to conventional histology?;

Study design:

60 patients from either HNPCC families or with familial CRC type X attending for colonoscopic surveillance will be examined twice, first with conventional white-light endoscopy and a second pass with pan-chromoscopy-guided endomicroscopy, in a segmental ‘back-to-back’ fashion. All polyps detected will be removed for histopathological analysis.

The following hypotheses will be tested:

Combined pan-chromoscopic colonoscopy and confocal endomicroscopy result in:

1. Higher adenoma yield, in particular of flat adenomas, mainly due to chromoendoscopy;

2. Improved diagnostic accuracy of neoplastic lesions, in particular:

a. reduction of overdiagnosis;

b. e.g. unnecessary polypectomy of non-neoplastic (low-risk) lesions;

c. reduction of underdiagnosis;

d. e.g. biopsy instead of resection of neoplastic lesions (in particular, the case of admixed serrated adenomas, or in case of sampling errors, etc.) as compared to conventional colonoscopy.

To prospectively assess the efficacy of combined pan-chromoendoscopy and confocal colonoscopy for the detection of neoplastic lesions in patients at high-risk for CRC.

Two issues will be addressed:

1. Does pan-colonic chromoendoscopy improve the diagnostic yield of colonic polyps (and in particular flat lesions) as compared to conventional colonoscopy?;

2. Does pan-colonic chomoendoscopy combined with confocal endomicroscopy result in higher diagnostic accuracy of colonic lesions as compared to conventional colonoscopy with biopsies?

N/A

Both techniques (conventional colonoscopy and confocal endomicroscopy) are routinely used in clinical practice at the Department of Gastroenterology of our hospital. In this regard, patients participating in the study will not undergo additional (invasive) examination. As the duration of the chromoscopy-guided confocal endomicroscopy procedure is somewhat longer than the standard procedure, the patient-burden will possibly increase, mainly due to the ‘back-to-back’ evaluation. The potential advantage is the achievement of higher diagnostic accuracy of preneoplastic lesions in this high-risk population.

During confocal endomicroscopy fluorescein will be administred intravenously, to generate confocal images. This is a safe contrast-agent which has been previously used for the diagnosis of ophtalmologic diseases (e.g. corneal infections). Additionally, fluorescein has been already used in more than 1000 patients undergoing confocal endomicroscopy, without relevant adverse events. Allergic reactions, in particular nausea seldom occur. Also, transient yellow discoloration of urine and skin may occur.




The general risks associated to the colonoscopic procedure are detailed in the endoscopy-folder of the GI Endoscopy Unit of the University Hospital Maastricht.