Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk factor of colorectal benign adenomas and advanced neoplasms. The aim of this large cohort study was to further investigate the prevalence of colorectal malignant neoplasm (CRMN) in patients with NAFLD and determine whether association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males and 945 females) who underwent a routine colonoscopy according to international colorectal cancer screening guideline were recruited. Nature of colorectal lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary logistic regression analysis was applied to explore the related associations. Prevalence of CRMN was 29.3% (77/263) in patients with NAFLD, which was significantly higher than 18.0% (369/2,052) in the control group (P<0.05). In addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid colon than in control group (14.3 vs. 11.9%). The incidence of highly-differentiated colorectal adenocarcinoma in NAFLD group was significantly higher than control group (62.3 vs. 9.8%). Univariate analysis showed that NAFLD had strong association with CRMN (OR 2.043; 95% CI 1.512-2.761; P<0.05). After adjusting for metabolic and other confounding factors, NAFLD remained as an independent risk factor for CRMN (OR 1.868; 95% CI 1.360-2.567; P<0.05). NAFLD was an independent risk factor for CRMN. Sigmoid carcinoma and highly differentiated colorectal adenocarcinoma were more commonly found in NAFLD. (ClinicalTrials.gov number, NCT01657773, website: http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1 ).

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using nextgeneration sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129-4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144-8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662-14.230)and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848-16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR-MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDS and could help identify those with worse-than-expected prognosis for more aggressive treatment. K E Y W O R D Slower-risk myelodysplastic syndromes, mutation burden, mutation status, prognosis, variant allele frequency | 581 JIANG et Al.

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