Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer

Background/AimsThe relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes.MethodsIn the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV).ResultsRegarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio [HR] 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women.ConclusionsThis study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.     

siRNA-mediated knockdown of the melanocortin 2 receptor accessory protein 2 (MRAP2) gene confers resistance to methylmercury on HEK293 cells

Methylmercury is a well-known environmental pollutant that causes serious disorders of the central nervous system as well as a range of other symptoms. We employed small interfering RNA (siRNA) to search for factors in ligand-dependent signal transduction pathways that may be involved in the development of methylmercury toxicity. Melanocortin 2 receptor accessory protein 2 (MRAP2) is involved in the melanocortin pathway. Using siRNA, we found that decreased expression of MRAP2 conferred strong methylmercury resistance in HEK293 cells.     

Differentiation of rickettsiae by groEL gene analysis

The nucleotide sequences (534 to 546 bp) of the groEL gene, which encodes the 60-kDa heat shock protein GroEL, from 15 rickettsial strains were determined and compared. In the phylogenetic tree created by the unweighted pair group method with arithmetic averages and the neighbor-joining method, rickettsial strains could be distinguished from Ehrlichia strains. Five spotted fever group strains, four typhus group strains, and six scrub typhus group (STG) strains were differentiated as distinct entities. Unlike gltA and ompA gene analyses, differentiation between members of the genus Rickettsia and the STG rickettsiae by groEL gene analysis was possible. In comparison with 16S rRNA gene analysis, the groEL gene has a higher degree of divergence among the rickettsiae. We therefore successfully developed rapid differentiation methods, PCR-restriction fragment length polymorphism analysis and a species-specific PCR, based on the groEL gene sequences. Four Korean isolates were identified by these methods and groEL gene analysis. The results suggest that the groEL gene is useful for the identification and characterization of rickettsiae.     

Korean guidelines for post-polypectomy colonoscopic surveillance

Post-polypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. However, because the medical resource is limited, and the first screening colonoscopy produces the greatest effect on reducing the incidence and mortality of colorectal cancer, there is a need to increase the efficiency of postpolypectomy surveillance. In the present report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy. Based on the results of review of the evidences, we elucidated the high risk findings of the index colonoscopy as follows: 1) 3 or more adenomas, 2) any adenoma larger than 10 mm, 3) any tubulovillous or villous adenoma, 4) any adenoma with high-grade dysplasia, and 5) any serrated polyps larger than 10 mm. In patients without any high-risk findings at the index colonoscopy, surveillance colonoscopy should be performed five years after index colonoscopy. In patients with one or more high risk findings, surveillance colonoscopy should be performed three years after polypectomy. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polyp removal, the patient's general condition, and family and medical history. This practical guideline cannot totally take the place of clinical judgments made by practitioners and should be revised and supplemented in the future as new evidence becomes available.     

Risk factors of nonadherence to colonoscopy surveillance after polypectomy and its impact on clinical outcomes: a KASID multicenter study

Background

An optimal surveillance program is important to prevent advanced colorectal neoplasm. In this context, we have evaluated the cumulative risk of high-risk adenoma (HRA) or colorectal cancer (CRC) according to surveillance interval time after polypectomy. In addition, we assessed risk factors for late surveillance to determine whether late surveillance can impact the risk of subsequent advanced colorectal neoplasm.

Methods

This was a multicenter retrospective cohort study involving 3562 subjects who had undergone removal of at least one adenoma at the index colonoscopy and who subsequently underwent a surveillance colonoscopy. The subjects were classified into an early, appropriate or late group depending on the timing of the surveillance colonoscopy, performed using modified U.S. guidelines.

Results

With 3% of the study population with LRA and HRA at the index colonoscopy going on to develop HRA or CRC, the estimated surveillance intervals calculated would be 6.3 [95% confidence interval (CI) 5.42–7.10] years and 3.1 (95% CI 2.61–4.45) years, respectively. The predictors of late surveillance were female gender [odd ratio (OR) 1.21; 95% CI 1.04–1.40], having undergone the procedure in small-to-medium-sized cities (OR 1.92; 95% CI 1.36–2.72) and HRA at index colonoscopy (OR 1.37; 95% CI 1.19–1.59). The risk factors for subsequent HRA or CRC were late surveillance (OR 1.34; 95% CI 1.03–1.74), male gender (OR 2.13; 95% CI 1.54–2.95), having undergone the procedure in small-to-medium-sized cities (OR 1.63; 95% CI 1.11–2.40) and HRA at index colonoscopy (OR 2.60; 95% CI 2.04–3.33).

Conclusions

Women, having undergone the procedure in small-to-medium-sized cities and the presence of an HRA at the index colonoscopy were found to be independent risk factors for late surveillance colonoscopy. Late surveillance is significantly predictive of subsequent HRA or CRC.

     

High-resolution vessel wall MRI for the evaluation of intracranial atherosclerotic disease

High-resolution vessel wall MRI (vwMRI) of the intracranial arteries is an emerging diagnostic imaging technique with the goal of evaluating vascular pathology. vwMRI sequences have high spatial resolution and directly image the vessel wall by suppressing blood signal. With vwMRI, it is possible to identify distinct morphologic and enhancement patterns of atherosclerosis that can provide important information about stroke etiology and recurrence risk. We present a review of vwMRI research in relation to intracranial atherosclerosis, with a focus on the relationship between ischemic stroke and atherosclerotic plaque T1 post-contrast enhancement or plaque/vessel wall morphology. The goal of this review is to provide readers with the most current understanding of the reliability, incidence, and importance of specific vwMRI findings in intracranial atherosclerosis, to guide their interpretation of vwMRI research, and help inform clinical interpretation of vwMRI. We will also provide a translational perspective on the existing vwMRI literature and insight into future vwMRI research questions and objectives. With increased use of high field strength MRI, powerful gradients, and improved pulse sequences, vwMRI will become standard-of-care in the diagnosis and prognosis of patients with cerebrovascular disease, making a firm grasp of its strengths and weakness important for neuroimagers.     

Three-dimensional late gadolinium enhancement imaging of the left atrium with a hybrid radial acquisition and compressed sensing

Purpose:

To develop and test a hybrid radial (stack of stars) acquisition and compressed sensing reconstruction for efficient late gadolinium enhancement (LGE) imaging of the left atrium.

Materials and Methods:

Two hybrid radial acquisition schemes, kx‐ky‐first and kz‐first, are tested using the signal equation for an inversion recovery sequence with simulated data. Undersampled data reconstructions are then performed using a compressed sensing approach with a three‐dimensional total variation constraint. The data acquisition and reconstruction framework is tested on five atrial fibrillation patients after treatment by radio‐frequency ablation. The hybrid radial data are acquired with free breathing without respiratory navigation.

Results:

The kz‐first radial acquisition gave improved image quality as compared to a kx‐ky‐first scheme. Compressed sensing reconstructions improved the overall quality of undersampled radial LGE images. An image quality metric that takes into account the signal, noise, artifact, and blur for the radial images was 35% (±17%) higher than the corresponding Cartesian acquisitions. Total acquisition time for 36 slices with 1.25 × 1.25 × 2.5 mm³ resolution was under 3 min for the proposed scheme.

Conclusion:

Hybrid radial LGE imaging of the LA with compressed sensing is a promising approach for obtaining images efficiently and offers more robust image quality than Cartesian acquisitions that were acquired without a respiratory navigator signal. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

Korean guidelines for postpolypectomy colonoscopy surveillance

Postpolypectomy surveillance has become a major indication for colonoscopy as a result of increased use of screening colonoscopy in Korea. In this report, a careful analytic approach was used to address all available evidences to delineate the predictors for advanced neoplasia at surveillance colonoscopy and we elucidated the high risk findings of the index colonoscopy as follows: 3 or more adenomas, any adenoma larger than 10 mm, any tubulovillous or villous adenoma, any adenoma with high-grade dysplasia, and any serrated polyps larger than 10 mm. Surveillance colonoscopy should be performed five years after the index colonoscopy for those without any high-risk findings and three years after the index colonoscopy for those with one or more high risk findings. However, the surveillance interval can be shortened considering the quality of the index colonoscopy, the completeness of polypectomy, the patient's general condition, and family and medical history.     

Association of interindividual differences in p14ARF promoter methylation with single nucleotide polymorphism in primary colorectal cancer

BACKGROUND: CpG island hypermethylation has been reported at the promoter region of many tumor suppressor genes in colorectal cancers. However, there are significant interindividual differences in the degree of DNA methylation in colorectal cancers. The objective of the current study was to understand whether single nucleotide polymorphisms (SNPs) around the promoter of a gene are implicated in the interindividual differences of CpG island hypermethylation. METHODS: Promoter methylation of the p14(ARF) gene and messenger RNA (mRNA) expression levels of p14(ARF), DNA methyltransferase 1 (DNMT1), and DNMT3b were investigated by using methylation-specific polymerase chain reaction (PCR) analysis (MSP) and quantitative real-time PCR analysis in fresh tissues from 188 patients with colorectal cancer. SNPs around the p14(ARF) promoter were genotyped in DNA from peripheral blood lymphocytes in 300 healthy individuals and in 188 patients with colorectal cancer by using matrix-assisted laser desorption/ionization mass spectrometry. RESULTS: p14(ARF) methylation was present in 61 of 188 colorectal cancers (32%). Fourteen SNPs among the 20 candidate SNPs were identified as monomorphic in the Korean population studied. Two individual SNPs (-4256 thymine to cytosine [T-->C] and -1477 guanine to adenine [G-->A]), which were in strong linkage disequilibrium (|D'|=0.99; correlation coefficient [r(2)]=0.95), were associated significantly with p14(ARF) methylation. Patients who had the CC variant at the-4256 locus or the AA variant at the -1477 locus had 2.42 times (95% confidence interval [95% CI], 1.07-5.46; P = .03) and 2.47 times (95% CI, 1.09-5.56; P= .03) greater risk of p14(ARF) methylation than patients who had the TT or GG homozygote, respectively, after adjusting for mRNA levels of DNMTs. Four major haplotypes were identified within a block (-4256 T-->C, -3631 T-->C, -1477 G-->A, and +20,188 T-->C). p14(ARF) promoter methylation also was associated significantly with the CCAT haplotype (odds ratio [OR], 8.31; 95% CI, 2.43-28.41; P= .0007) and the CTAC haplotype (OR, 9.71; 95% CI, 1.09-86.24; P= .04). CONCLUSIONS: The current results suggested that SNPs around the p14(ARF) promoter region may be responsible for the interindividual susceptibility to p14(ARF) promoter methylation among individuals with colorectal cancer.