Acetic Acid-Indigo Carmine Chromocolonoscopy for Proximal Serrated Lesions: A Randomized, Three-Arm Colonoscopy Study

Objectives: Aggressive colorectal cancer (CRC) frequently originates from serrated lesions (SLs), particularly in the proximal colon, which are challenging to detect using standard screening colonoscopy. Although duplicate examinations or chromocolonoscopies are recommended for detecting proximal SLs, evidence from randomized trials is limited. We evaluated the effectiveness of tandem colonoscopy with an acetic acid-indigo carmine mixture (AIM) for detecting SLs in the proximal colon compared to white-light imaging (WLI) and indigo carmine (IC). Methods: This three-arm, multicenter, randomized controlled trial involving nine institutions enrolled patients undergoing colonoscopy and assigned them randomly to the WLI, IC, or AIM group. The primary outcomes were the SL-detection rate (SDR) of proximal lesions during the second examination (SDR^2nd) and SL additional rate (SAR). Secondary outcomes included the detection and additional rates of other polyps, factors contributing to SAR, and complications. Results: Between 2021 and 2024, 1,319 participants with 1,267 polyps were included in the analysis. With AIM, the SDR^2nd and SAR were significantly higher compared to WLI or IC (WLI vs. AIM: 2.7% vs. 14.0%, p<.001; IC vs. AIM: 7.9% vs. 14.0%, p=.002, and WLI vs. AIM: 22.4% vs. 69.3%, p<.001; IC vs. AIM: 45.8% vs. 69.3%, p=.001). AIM conferred a higher adenoma-detection rate (ADR)^2nd than with WLI (10.5% vs. 24.7%; p<.001) and was an independent factor for SAR (odds ratio [95% confidence interval]: 7.79 [3.76–17.08]). No major adverse events were observed. Conclusions: AIM significantly improved proximal colon SDRs and outperformed WLI and IC. The relationship between SDR and CRC incidence warrants further investigation.