Tumor deposit may be an independent adverse prognostic factor for stage II and III N1 colorectal cancer.

A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP status was classified according to the number of methylated genes and was correlated with the clinicopathological features, including the concomitant polyps in and around the tumors. The frequency of aberrant methylation in each CRC showed a bimodal pattern, and the CRCs were classified as CIMP-high (CIMP-H), CIMP-low (CIMP-L) and CIMP-negative (CIMP-N). CIMP-H was associated with aberrant methylation of MLH1 (P=0.005) and with an improved recurrence-free survival (RFS) rate following curative resection compared with CIMP-L/N (five-year RFS rate, 93.8 vs. 67.1%; P=0.044), while CIMP-N tumors were associated with frequent distant metastases at diagnosis (P=0.023). No concomitant serrated lesions were present in the tumors, whereas conventional adenoma was contiguous with 11 (10.6%) of 104 CRCs, including four CIMP-H CRCs. CIMP-H was classified in CRCs by a novel CIMP marker panel and the presence of concomitant tumors revealed that certain CIMP-H CRCs may have arisen from conventional adenomas.

Oscillation of the vocal folds makes a sound source of the human voiced sound. Understanding of the oscillation mechanism, which is a complex flow-structure interaction problem in the airway, is crucial for considering clinical diagnosis of voice disorders. However, details of the oscillation mechanism are still unclear partly because, from a fluid mechanical viewpoint, the effect of oscillation of the vocal fold wall during the phonation on airflow behaviors remains elusive. In the present study, flow characteristics in a sinusoidally-oscillating constriction mimicking the vocal fold were investigated by numerical and experimental approaches. The numerical analyses focused in particular on the effect of constriction oscillation on flow separation demonstrated that the flow separation point moves continuously and periodically in a frequency-dependent manner. In the experimental study, an apparatus was newly designed, with a view to detect the oscillation-induced movement of the flow separation point, to enable detailed measurement of pressure distribution along the constriction with an interval of 2 mm that is synchronized with measurement of constriction displacement. Although movement of the separation point as seen in the numerical analyses was not detected by this limiting resolution of the apparatus, we obtained pressure-width relations that is partly contrary to the numerical results but is presumably dependent on the inlet boundary condition. These findings indicate that appropriate evaluations of separation point and inlet boundary conditions are key factors to characterize the flow in oscillating constriction, which is crucial for better understanding of the vocal fold mechanics.

Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.

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