Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients’ ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

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The large-scale vortex structures under spilling and plunging breakers are investigated, using a fully three-dimensional large-eddy simulation (LES). When an overturning jet projecting from the crest in a breaking wave rebounds from the water surface ahead, the vorticity becomes unstable in a saddle region of strain between the rebounding jet and a primary spanwise vortex, resulting in spanwise undulations of the vorticity. The undulations are amplified on a braid in this saddle region, leading to a vortex loop with counter-rotating vorticity. This vortex loop consequently envelops adjacent primary vortices, to form a typical rib structure. This rib component (the stretched vortex loop) in the large-scale vortex structure, which intensifies in the strains associated with the multiple primary vortices generated throughout the splash-up cycle, appears to be the previously found obliquely descending eddy.

Background The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. Patients and methods We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria.Results Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3-and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3-and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapsefree survival. Conclusions To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.