Enhancing the efficacy of colonoscopy in Lynch syndrome: the search for the holy grail continues

Abstract

share the results from their randomized controlled trial assessing the impact of proximal colon chromoendoscopy for the detection of neoplasia at baseline and follow-up colonoscopy in patients with Lynch syndrome (LS) performed across 6 centers in the Netherlands. In the trial, indigo carmine chromoendoscopy application in the proximal colon was compared with standard white-light endoscopy (WLE) in 246 mismatch repair gene mutation carriers. Although chromoendoscopy led to a significantly increased median withdrawal time (19 vs 12 minutes), no improvement in the number of patients detected with neoplasia was observed (30% vs 27%). In a subgroup analysis, chromoendoscopy was not associated with the detection of proximal adenomas (24% vs 16%) but more than doubled the detection of "nuisance" lesions (56% vs 26%), including polypoid normal mucosa and lymphoid follicles. At the end of the study, one quarter of the study patients were excluded, and end-of-study colonoscopy was performed in only 186 patients at a median of 2 years after the baseline examination. At that time, the included patients had their proximal colons again sprayed with chromoendoscopy. No difference was noted in the overall rate of neoplasia detection (26% vs 28%) or in neoplasms detected per colonoscopy (0.39 vs 0.41). Subgroup analysis of findings in the proximal colon also yielded no significant differences. The proximal adenoma detection rate (ADR) was 22% in each arm. Importantly, colorectal cancer (CRC) was diagnosed at the 2-year colonoscopy in 4 patients (2.1%); 3 in the chromoendoscopy at baseline group, and 1 in the WLE at baseline group.LS is a hereditary cancer risk predisposition syndrome due to defective DNA mismatch repair (MMR). The diagnosis is made in a patient by the detection of a germline pathogenic variant in 1 of the MMR genes (MLH1, MSH2, MSH6, PMS2) or EPCAM. Data demonstrate that the cumulative risk of CRC by age 70 varies by mutation and gender. Risks are lower in women than in men, lowest in those with a PMS2 mutation, intermediate in those with MSH6, and highest in those with MLH1 and MSH2 pathogenic mutation carriers. CRC risk derived from studies excluding PMS2 and accounting for ascertainment bias demonstrate cumulative risks ranging between 27% and 45% for men and between 22% and 38% for women. 2 Guidelines recommend surveillance colonoscopy every 1 to 2 years starting at ages 20 to 25, or 2 to 5 years before the earliest CRC in the family if diagnosed before age 25. 3,4 The frequent surveillance intervals suggested are due to reported rates of rapid development of advanced neoplasia and CRC, particularly in the proximal colon and occurring within 2 to 3 years of previous colonoscopy. [5][6][7] Recent data from Europe demonstrate a 10-year cumulative CRC incidence of up to 18.4% in patients undergoing close colonoscopic surveillance. 8 Surprisingly, no difference in the incidence or stage of CRC was observed between countries with an annual, versus 1-year to 2year, or 2-year to 3-year, surveillance interval. These...

Incident colorectal cancer in Lynch syndrome is usually not preceded by compromised quality of colonoscopy

“…Adenoma miss rate was especially high (33%) in patients with high risk of CRC [24]. On the other hand, as many of these studies reporting high ADRs have been tandem studies, CE with substantially longer withdrawal times being the latter and preceded by WLE of the two, which may have accounted for the higher detection rate [7].…”

“…The findings indicate that the effectiveness of colonoscopy in clinical practice is lower than was interpreted from early clinical intervention studies [5,6]. The following discussion has raised questions of the historical quality of colonoscopy as a factor contributing to poor preventive performance [7]. On the other hand, alternative hypotheses based on different tumor biology have been proposed: some LS-associated CRCs arise directly from mismatch repair deficient crypt foci and may not be preceded by a macroscopically distinct precursor adenoma [8,9].…”