Reproducibility and accuracy of visual estimation of polyp size in large colorectal polyps.

BACKGROUND: Previous studies indicate that visual size estimation (in situ) of polyp size tends to differ from postfixation measurements, which effects allocation to surveillance intervals. Little is known about interobserver variation of in-situ measurements of large polyps. The primary objective was to assess interobserver variation of in situ measurements of large colorectal polyps. Secondary objectives were the agreement of in situ measurements with postfixation measurements, and the agreement on detection of ≥20 mm polyps between these measurements. MATERIAL AND METHODS: Interobserver variability of in situ polyp size measurements was assessed between a diagnostic colonoscopy and the secondary therapeutic colonoscopy by dedicated endoscopists, in patients that were referred for an advanced polypectomy. After excision pre- and postfixation polyp sizes were measured with a ruler in three dimensions. RESULTS: A total of 40 patients, with 45 polyps, were included in the study. The average difference between the two in situ measurements was 2.4 mm (95% confidence interval (CI): -0.4-5.2). The differences between the first in situ, second in situ and pre-fixation measurement in comparison to postfixation measurements were 1.8 mm (95% CI: -1.2-4.9), 0.1 mm (95% CI: -1.5-1.8) and 1.0 mm (95% CI: -0.2-2.2). Cohen's Kappa on detection of ≥20 mm polyps in agreement with postfixation measurements was 0.65 in the primary and 0.88 in the secondary in situ measurements. CONCLUSION: This study shows a variation between in situ size measurements of large polyps. Improvements in daily clinical routines can be made by using an instrument to compare polyp size with and refraining from rounding sizes up or down. A randomized controlled trial assessing which instruments should be used for in-situ measurements of large polyps is warranted, in order to optimize size measurements of large colorectal polyps.

Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer.

OBJECTIVE: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. METHODS: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. RESULTS: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients. CONCLUSION: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.