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.

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SUMMARYBackground: The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic-resistant strains and the problem of re-treatment in cases of eradication failure. Aim: To perform drug sensitivity testing for metronidazole in 92 H. pylori-positive patients who had failed eradication treatment with first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, and were administered metronidazolecontaining second-line therapy.

In 10 years after H. pylori eradication, atrophy at all sites and IM in the lesser curvature of the corpus gradually and significantly decreased. These results suggest that the improvement of gastric atrophy and IM might have association with the reduction of gastric cancer occurrence.

SUMMARYBackground: The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure. Aim: To compare the eradication rates of triple therapy using amoxicillin (A), clarithromycin (C) and rabeprazole (R) or lansoprazole (L) against clarithromycinsensitive and clarithromycin-resistant strains. Methods: Two hundred and ninety-five patients were randomly divided into four groups and treated for 1 week: 147 cases were treated with RAC, i.e. 49 cases with R20C400 (10 mg R + 750 mg A + 200 mg C, twice daily), 48 cases with R40C400 (20 mg R + 750 mg A + 200 mg C, twice daily) and 50 cases with R40C800 (20 mg R + 750 mg A + 400 mg C, twice daily); 148 cases with treated with LAC (30 mg L + 750 mg A + 200 mg C, twice daily).