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Earlier detection of colorectal cancer (CRC) results in improved survival. Existing non-invasive biomarkers have suboptimal accuracy. Neurotensin (NTS) is involved in CRC carcinogenesis. This study evaluated the diagnostic potential of plasma NTS for colorectal polyps and cancers. Participants were selected based on national CRC referral guidelines. All subjects underwent colonoscopy. Average plasma concentrations were compared across different diagnostic groups. Predictors for detecting colorectal neoplasia were identified. Receiver operator characteristic (ROC) curve analysis assessed the diagnostic accuracy of NTS. An independent biobank was used as validation group. Of 165 participants, 46 had polyps or CRC. Significantly higher plasma NTS was found in the colonic neoplasia group (603.6 pg/ml vs. 407.2 pg/ml, p < 0.01). Risk factors for colonic polyps or cancers included Loge (plasma NTS concentration) (OR, 2.73; 95% CI, 1.33–5.59, p < 0.01), loge (Age) (OR, 15.49; 95% CI, 2.67–89.66, p < 0.01) and cigarette smoking (OR, 3.49; 95% CI, 1.31–9.26, p = 0.01). Plasma NTS had an optimal sensitivity of 60.4% and specificity of 71.6% for the diagnosis of colorectal polyps and cancers. Similar diagnostic accuracy was obtained in the validation group. Plasma NTS has the potential to be a non-invasive biomarker for colorectal neoplasia. It appears to be more accurate than existing blood markers and is unique in being able to detect precancerous polyps.

Background No head-to-head randomized controlled trials have demonstrated the superiority of one colorectal screening modality over another in reducing colorectal cancer mortality. We conducted a pilot randomized controlled trial of fecal occult blood testing (FOBT), optical colonoscopy (OC), and virtual colonoscopy (VC), to inform the planning of a larger evaluative trial. Methods Eligible patients (aged 50 to 70) were recruited from five primary care practices in Hamilton, ON, Canada, between March 23, 2010 and August 11, 2010, and randomized 1:1:1 in a parallel design using an automated, centralized telephone service to either FOBT, OC, or VC. To reflect conventional practice, patients received no additional reminders to complete their allocated screening test beyond those received in usual practice. The primary outcome was completion of the assigned screening procedure. Results of the index test and any follow-up investigations were ascertained at 6 months. Participants, caregivers, and outcome assessors were not blinded to group assignment. The trial was stopped early due to lack of ongoing funding. Results A total of 198 participants were enrolled, of whom 67 were allocated to FOBT, 66 to OC, and 65 to VC. The allocated screening procedure was completed by 43 (64 %) subjects allocated to FOBT (95 % confidence interval [CI], 52–75 %), 53 (80 %) subjects allocated to OC (95 % CI, 69–88 %), and 50 (77 %) subjects allocated to VC (95 % CI, 65–85 %); because the trial stopped early, we had insufficient statistical power to detect clinically relevant differences in completion rates. During 6 months follow-up, colorectal adenomas were detected in 0 (0 %) subjects allocated to FOBT, 12 (18 %) subjects allocated to OC, and 2 (3 %) subjects allocated to VC. One subject in the OC arm had histological evidence of high-grade dysplasia. No subjects were diagnosed with colorectal cancer. Conclusions In this pilot randomized controlled trial of colorectal cancer screening in a primary care setting, 64–80 % of subjects completed their allocated screening test. These findings may be of value to investigators planning clinical trials to evaluate the effectiveness of colorectal cancer screening. Trial registration ClinicalTrials.gov NCT00865527. https://clinicaltrials.gov/ct2/show/NCT00865527

Numerous studies have shown that early screening for the presence of pre-cancerous colon polyps and their subsequent removal decreases the risk of developing colon cancer. Colonoscopy is currently the most effective screening method, but due to the invasive nature of the procedure many patients avoid forgo testing. Futhermore, the procedure itself requires perfect execution by the gastroenterologist. Against this backdrop, a non-invasive blood screening method for the detection of colon polyps that has higher sensitivity than current screening techniques would be beneficial in the early identification of patients at risk for colon cancer. A prospective, double-blinded, controlled clinical study was designed to demonstrate the diagnostic performance of Polyp Specific Polymer analysis, a novel laboratory methodology. The primary objective of this clinical trial was to estimate the diagnostic accuracy of the Polyp Specific Polymer analysis for colon polyps using colonoscopy and histological tests as the diagnostic accuracy standards. Secondary objectives of this trial included estimating positive and negative predictive values for colon polyps, investigating reliability, determining covariates influencing diagnostic accuracy and obtaining absolute and relative frequencies of valid test results. In patients undergoing screening colonoscopy and histology examination, a sensitivity of 72.4% and a specificity of 62.3% could be proven. These results indicate that using this improved screening method it is possible to effectively identify the highest-risk candidates for endoscopy, thereby advancing the goal of decreasing the incidence or mortality of colorectal cancer in the selected population. Moreover, this diagnostic tool has potential socio-economic implications, conserving healthcare resources by enabling higher patient selectivity for endoscopy and eventual transfer to curative prevention via polypectomy. By combining the best-established low-risk screening elements together with a validated, highly sensitive blood test as described in this study, a steadfast increase in the estimation of colorectal cancer-risk before colonoscopy can be expected.

Galectin-3 (Gal-3) secreted by activated macrophages is involved in inflammation, fibrosis, and tumorigenesis. It is considered a potential biomarker and therapeutic target. This study assessed the association between serum Gal-3, type 2 diabetes (T2D), and colorectal polyps (CRPs). In this cross-sectional study, 80 non-cancer patients undergoing colonoscopy were divided into four subgroups based on T2D and CRP status. Serum Gal-3 and metabolic parameters were measured. All patients’ mean serum Gal-3 level was 13.63 ng/mL. Gal-3 levels were significantly higher in T2D+ than in the T2D− group (14.93 ng/mL, p = 0.02). Gal-3 concentration correlated significantly with age (rho = 0.281; p = 0.012), gender (rho = 0.220; p = 0.049), serum peptide C levels (rho = 0.957; p = 0.006), and serum IGF-1 levels (rho = −0.417; p < 0.001) in all patients, and for patients T2D-, it also correlated significantly with fasting plasma glucose levels (rho = −0.406; p = 0.009). A logistic regression analysis of the risk of polyps was conducted (CRP+ vs. CRP−) considering factors such as gender, age, body weight, waist circumference, T2D, HOMA-IR, insulin, API, IGF-1, total cholesterol, and Gal-3. Gal-3 serum was shown to be a strong independent predictor of CRPs regardless of the presence of T2D+ (p = 0.031). Gal-3 may correlate with the development of CRPs and might be a candidate biomarker of CRPs/cancer development.

BackgroundEarly detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology.AimsTo investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP.MethodsA prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 μg hemoglobin (Hb)/g feces.ResultsOne thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20 μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 μg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT.ConclusionsBoth FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Background Hyperlipidaemia may be a potential risk factor for the occurrence of intestinal polyps. This study aimed to evaluate correlation between lipidaemia and the formation of colorectal polyps. Methods One hundred and fourteen patients with colorectal polyps and forty-eight healthy controls were included in this study. Colonoscopies were performed for all patients and controls within 1 week before blood samples were taken. The concentrations of serum lipids and lipoproteins were measured simultaneously using an automatic biochemical analyser. The colorectal lesions were classified based on pathological characteristics, and four types were identified in the study: hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA) and adenoma with high-grade dysplasia (A-HGD). Advanced adenoma was classified according to the number, size and histological type of polyps. Results The value of low-density lipoprotein cholesterol (LDL-C) was significantly higher in the group with advanced adenoma than in the controls ( p  < 0.05). Moreover, the LDL-C values in the HP and TA groups were higher when compared to that of controls ( p  < 0.05). Obesity, age, and increased TG and LDL-C were independent risk factors for the formation of colorectal polyps. The cut-off values of triglyceride (TG) and LDL-C to distinguish polyp patients from healthy controls were 0.96 mmol/L (AUC = 0.604, p  = 0.036) and 3.05 mmol/L (AUC = 0.654, p  = 0.002). The combined use of increased LDL-C and TG levels to distinguish polyp patients was effective, with a sensitivity of 50.0% and a specificity of 89.6% (AUC = 0.733, p  < 0.01). Conclusions Colorectal polyps are more often found in obese and older patients. Increased LDL-C and TG were correlated with the occurrence of polyps. Combination of the two serum indicators was useful to assess risk of colorectal lesions, maybe more effective in screening hyperplastic polyp, tubular adenoma and advanced adenoma.

Background The CRP-albumin-lymphocyte (CALLY) index has potential clinical value as a novel marker integrating inflammatory, nutritional and immune status in the development of colorectal polyps. This study examined whether gender factors influence the association between CALLY and colorectal polyps; in addition to elucidating whether metabolic pathways mediate this relationship. Methods This is a cross-sectional study including 5409 adult health screening participants who completed colonoscopy. Logistic regression analysis, correlation analysis, linear regression analysis and restricted cubic spline modeling, and mediation analysis were employed to investigate the intricate associations between CALLY index, inflammatory biomarkers, metabolic factors and colorectal polyps. Results A total of 2201 subjects were diagnosed with colorectal polyps. Logistic regression analysis showed that higher CALLY index quartiles were inversely correlated with colorectal polyp prevalence (OR = 0.83,95% CI = 0.70–0.98, P  = 0.025), and that this association was more pronounced in the female population (OR = 0.67,95% CI = 0.50–0.91, P  = 0.011), while no significant association was observed in males ( P  > 0.05). Mediation analyses showed partial mediation of TyG (mediated effect: 15.14%, P  < 0.01) and Non-HDL-C (mediated effect: 8.20%, P  < 0.01) between CALLY index and colorectal polyps, whereas females showed stronger mediation of TyG (mediated effect: 15.49%, P  = 0.020). Conclusions There were sex differences in the negative association of CALLY index with colorectal polyps, with a stronger association in women; the glucose metabolism (TyG) and lipid metabolism (Non-HDL-C) pathways partially mediated the association, and the mediating effect of TyG was more significant in women.

Background The platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) level are markers that have been reported to predict the histological type of various tumors, and here, we evaluated their utility in predicting colorectal polyp histological types. Methods We retrospectively reviewed 172 patients with colorectal polyps who underwent endoscopic polypectomy. The associations between histological type and clinicopathologic parameters were assessed by multivariate analysis. Results The optimal PLR and CRP cut-off values were 113.32 and 0.39, respectively. The PLR ( P  = 0.002) and CRP ( P  = 0.009) values were associated with the histological type according to the univariate analysis, whereas low PLR ( P  ≤ 0.001) and CRP ( P  = 0.017) values were independent risk factors in the multivariate analysis together with maximum tumor diameter ( P  ≤ 0.001) and tumor number ( P  = 0.0014). Conclusions Preoperative PLR and CRP are correlated with the colorectal polyp histological type.

The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04). Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

Background The relationship between serum lipids and colorectal polyps (CP) remains unclear due to inconsistent findings across prior studies. This study aimed to comprehensively explore the relationship between serum lipid levels and CP risk by using real-world clinical data. Methods By utilizing retrospective data from a tertiary hospital from 2015 to 2024, multivariate logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed to assess the association between serum lipids and CP. Additionally, the mediating role of inflammation-related indices in the relationship between serum lipids and CP was examined. Results Triglyceride (TG) and total cholesterol (TC) were positively associated with CP risk ( P  < 0.05). RCS analysis revealed a nonlinear dose–response relationship between TG and CP risk ( P for overall < 0.001, nonlinear P  < 0.05), with a threshold value of 0.93 mmol/L. Significant interaction effects were observed between TG and TC and gender in relation to CP development. Inflammation-related indices mediated the association between high-density lipoprotein cholesterol and TC with CP risk ( P  < 0.05). Conclusion This study highlights the potential clinical utility of TG and TC as modifiable biomarkers for CP risk. Future prospective studies are warranted to validate these findings and to explore targeted lipid-modifying interventions for high-risk populations.