Objective Endoscopic Analysis with Linked Color Imaging regarding Gastric Mucosal Atrophy: A Pilot Study

Objectives. We aimed to determine whether linked color imaging (LCI), a new image-enhanced endoscopy that enhances subtle differences in mucosal colors, can distinguish the border of endoscopic mucosal atrophy. Methods. This study included 30 patients with atrophic gastritis. In endoscopy, we continuously took images in the same composition with both LCI and white light imaging (WLI). In each image, the color values of atrophic and nonatrophic mucosae were quantified using the International Commission on Illumination 1976 (L∗, a∗, b∗) color space. Color differences at the atrophic border, defined as Euclidean distances of color values between the atrophic and nonatrophic mucosae, were compared between WLI and LCI for the overall cohort and separately for patients with Helicobacter pylori infection status. Results. We found that the color difference became significantly higher with LCI than with WLI in the overall samples of 90 points in 30 patients. LCI was 14.79 ± 6.68, and WLI was 11.06 ± 5.44 (P<0.00001). LCI was also more effective in both of the Helicobacter pylori-infected group (P=0.00003) and the Helicobacter pylori-eradicated group (P=0.00002). Conclusions. LCI allows clear endoscopic visualization of the atrophic border under various conditions of gastritis, regardless of Helicobacter pylori infection status

Association between Gastric Cancer Risk and Serum Helicobacter pylori Antibody Titers

Background/Aims. It is difficult to confirm the accurate cutoff value to diagnose Helicobacter pylori (Hp) infection using commercial serology kits. It is reported that there were many cases with present/past infection that even the serum Hp-IgG antibody (HpAb) titers were below the cutoff value (e.g., 10 U/mL for E-Plate®), suggesting that we might overlook many gastric cancer (GC). We investigated an association between gastric cancer risk and serum Helicobacter pylori antibody titers. Methods. We conducted a primary screening between 2014 and 2015. We performed gastroendoscopy if HpAb titers were ≥3.0 U/mL (i.e., more than measurable limit, E-Plate). These patients were divided into two groups: HpAb = 3.0–9.9 U/mL (“negative-high” group) and HpAb ≥ 10 U/mL; cutoff value (“over-10 U/mL” group). Hp infection status was investigated, and the number of GC patients was counted. Results. Among the 3321 subjects in the primary screening, 56.9% (1891/3321) showed HpAb titers ≥3.0 U/mL; 1314 patients underwent gastroendoscopy. Ten were GC. 421 patients were “negative-high” group; two were GC. After evaluating 381 patients for Hp infection, 22.6%/60.6% was with present/past infection among the “negative-high” group. Conclusion. We also found a correlation between HpAb titers and Hp infection status. “Negative-high” group has a risk of GC

A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression