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Genetic Predisposition to Colon and Rectal Adenocarcinoma Is Mediated by a Super-enhancer Polymorphism Coactivating CD9 and PLEKHG6.
Ke, J, Tian, J, Mei, S, Ying, P, Yang, N, Wang, X, Zou, D, Peng, X, Yang, Y, Zhu, Y, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(4):850-859
Abstract
BACKGROUND Genome-wide association studies (GWAS) have identified dozens of loci associated with colon and rectal adenocarcinoma risk. As tissue-specific super-enhancers (SE) play important roles in tumorigenesis, we systematically investigate SEs and inner variants in established GWAS loci to decipher the underlying biological mechanisms. METHODS Through a comprehensive bioinformatics analysis on multi-omics data, we screen potential single-nucleotide polymorphisms (SNP) in cancer-specific SEs, and then subject them to a two-stage case-control study containing 4,929 cases and 7,083 controls from the Chinese population. A series of functional assays, including reporter gene assays, electrophoretic mobility shift assays (EMSA), CRISPR-Cas9 genome editing, chromosome conformation capture (3C) assays, and cell proliferation experiments, are performed to characterize the variant's molecular consequence and target genes. RESULTS The SNP rs11064124 in 12p13.31 is found significantly associated with the risk of colon and rectal adenocarcinoma with an odds ratio (OR) of 0.87 [95% confidence interval (CI), 0.82-0.92, P = 8.67E-06]. The protective rs11064124-G weakens the binding affinity with vitamin D receptor (VDR) and increases the enhancer's activity and interactions with two target genes' promoters, thus coactivating the transcription of CD9 and PLEKHG6, which are both putative tumor suppressor genes for colon and rectal adenocarcinoma. CONCLUSIONS Our integrative study highlights an SE polymorphism rs11064124 and two susceptibility genes CD9 and PLEKHG6 in 12p13.31 for colon and rectal adenocarcinoma. IMPACT These findings suggest a novel insight for genetic pathogenesis of colon and rectal adenocarcinoma, involving transcriptional coactivation of diverse susceptibility genes via the SE element as a gene regulation hub.
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Video-Based Assessments of Colonoscopy Inspection Quality Correlate With Quality Metrics and Highlight Areas for Improvement.
Duloy, A, Yadlapati, RH, Benson, M, Gawron, AJ, Kahi, CJ, Kaltenbach, TR, McClure, J, Gregory, DL, Keswani, RN
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(4):691-700
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Abstract
BACKGROUND & AIMS Adenoma detection rate (ADR) and serrated polyp detection rate (SDR) vary significantly among colonoscopists. Colonoscopy inspection quality (CIQ) is the quality with which a colonoscopist inspects for polyps and may explain some of this variation. We aimed to determine the relationship between CIQ and historical ADRs and SDRs in a cohort of colonoscopists and assess whether there is variation in CIQ components (fold examination, cleaning, and luminal distension) among colonoscopists with similar ADRs and SDRs. METHODS We conducted a prospective observational study to assess CIQ among 17 high-volume colonoscopists at an academic medical center. Over 6 weeks, we video-recorded >28 colonoscopies per colonoscopist and randomly selected 7 colonoscopies per colonoscopist for evaluation. Six raters graded CIQ using an established scale, with a maximum whole colon score of 75. RESULTS We evaluated 119 colonoscopies. The median whole-colon CIQ score was 50.1/75. Whole-colon CIQ score (r=0.71; P<.01) and component scores (fold examination r=0.74; cleaning r=0.67; distension r=0.77; all P<.01) correlated with ADR. Proximal colon CIQ score (r=0.67; P<.01) and component scores (fold examination r=0.71; cleaning r=0.62; distension r=0.65; all P<.05) correlated with SDR. CIQ component scores differed significantly between colonoscopists with similar ADRs and SDRs for most of the CIQ skills. CONCLUSION In a prospective observational study, we found CIQ and CIQ components to correlate with ADR and SDR. Colonoscopists with similar ADRs and SDRs differ in their performance of the 3 CIQ components-specific, actionable feedback might improve colonoscopy technique.
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Short-term and oncologic outcomes of laparoscopic and open complete mesocolic excision and central ligation.
Kim, IY, Kim, BR, Choi, EH, Kim, YW
International journal of surgery (London, England). 2016;:151-157
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Abstract
PURPOSE To evaluate the pathologic, short-term and oncologic outcomes of laparoscopic and open complete mesocolic excision (CME) and central ligation for right-sided colon cancer. METHODS All patients (n = 215) underwent elective CME either by open surgery (n = 99) or laparoscopy (n = 116). RESULTS Mean number of retrieved lymph nodes (31 vs. 27, p = 0.012) was greater in the open CME group. Between the open and laparoscopic CME groups, there were no differences of length of the specimen (44.3 cm and 43.2 cm), ileum (14 cm and 13.3 cm), or colon (30.3 cm and 29.8 cm), respectively. Proximal and distal margins were similar. Mean operative time was similar between the open and laparoscopic CME groups (175 min vs. 178 min). The rate of 30-day postoperative complications (36.4% vs. 23.3%, p = 0.036) was higher in the open CME group. There were no differences in 3-year overall survival rates (86.9% vs. 95.5% in stage II disease and 70.2% vs. 90.7% in stage III disease) or recurrence-free survival rates (84.5% vs. 84.8% in stage II disease and 64.2% vs. 68.9% in stage III disease) between the open and laparoscopic CME groups. CONCLUSIONS Pathologic (specimen lengths, resection margin lengths, number of lymph nodes, and R0 resection) and oncologic outcomes of the laparoscopic CME group were comparable. Moreover, laparoscopic CME conferred short-term benefits in terms of lower rates of postoperative complications, reduced time to soft diet, and reduced length of hospital stay. Based on these results, laparoscopic CME can be considered as a routine elective approach for right-sided colon cancer.