Exploring Vitamin D Deficiency and IGF Axis Dynamics in Colorectal Adenomas.

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.

Cost-Utility Analysis of Berberine Chemoprevention for Colorectal Cancer After Polypectomy.

Background Chemoprevention, such as berberine, has been developed as an alternative or complementary strategy to colonoscopy surveillance and has shown promise in reducing the morbidity and mortality of colorectal cancer. This study aims to evaluate the cost-effectiveness of berberine for postpolypectomy patients from the US third-party payer. Methods A Markov microsimulation model was developed to compare the cost and efficacy of berberine to no intervention, colonoscopy, and the combination of berberine and colonoscopy in postpolypectomy patients. Results After simulating 1 million patients, the study found that colonoscopy alone had a mean cost of $16,391 and mean quality-adjusted life-years (QALYs) of 16.03 per patient, whereas adding berberine slightly reduced the mean cost to $15,609 with a mean QALY of 16.05, making it a dominant strategy. Berberine therapy alone was less effective than colonoscopy alone, with a higher mean cost of $37,480 and a mean QALY of 15.32 per patient. However, berberine therapy was found to be a dominant strategy over no intervention. Conclusions Adding berberine to colonoscopy is the most cost-saving and effective approach for postpolypectomy patients. For patients who refuse or have limited access to colonoscopy, berberine alone is likely to be a dominant strategy compared to no intervention.

Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study.

OBJECTIVE: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. DESIGN: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up. RESULTS: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87). CONCLUSION: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.

Increased risk of colorectal adenomas with metabolic-associated fatty liver disease components.

BACKGROUND: Metabolic (dysfunction)-associated fatty liver disease is the most common liver disease related to various metabolic disorders. Colorectal adenomas are related to metabolic dysregulation. Despite the proposed association between non-alcoholic fatty liver disease and colorectal adenomas, the influence of metabolic-associated fatty liver disease on colorectal adenomas has yet to be investigated. Our study investigates the relationship between metabolic-associated fatty liver disease and colorectal adenomas and evaluates the predictive value of fatty liver index for colorectal adenomas. METHODS: A retrospective cross-sectional study was conducted on 650 inpatients at Qinghai Provincial People's Hospital. All participants underwent colonoscopy, abdominal ultrasound or CT, relevant laboratory tests, and physical examinations to ascertain baseline characteristics and overall health status. Multivariate logistic regression analysis examined the relationship between metabolic-associated fatty liver disease and colorectal adenomas. Lastly, the ability to identify, accuracy, and clinical applicability of predicting colorectal adenomas through fatty liver index were assessed using receiver operating characteristic curve area under the curve, calibration curve, and decision curve analysis. RESULT: In both the colorectal adenomas and control groups, the prevalence of metabolic-associated fatty liver disease was 62.1 % and 35.7 %, respectively. Multivariate analysis indicates that metabolic-associated fatty liver disease was independently correlated with an increased risk of colorectal adenomas (OR, 1.565; 95 % CI, 1.057-2.319; P < 0.05). Further analysis revealed that the risk of colorectal adenomas increased with an increasing quantity of metabolic components in metabolic-associated fatty liver disease (Ptrend < 0.001). The area under the curve of the fatty liver index predictive model was 0.838, with a 95 % CI of 0.807-0.869. The calibration curve indicated excellent agreement, and the decision curve analysis revealed a higher net benefit. CONCLUSION: The risk of colorectal adenomas was associated with metabolic-associated fatty liver disease, and the risk of developing colorectal adenomas increased with the presence of more metabolic-associated fatty liver disease metabolic components. Furthermore, fatty liver index served as a predictive indicator for screening colorectal adenomas.

The Association between Red Meat Consumption and Advanced Colorectal Adenomas in a Population Undergoing a Screening-Related Colonoscopy in Alberta, Canada.

The association between red meat consumption and colorectal cancer has been rigorously examined. However, a more comprehensive understanding of how the intake of unprocessed red meat contributes to the development of early precancerous colorectal lesions, such as advanced colorectal adenomas (ACRAs), requires further investigation. We examined the associations between different types of red meat intake and ACRAs in a sample population of 1083 individuals aged ≥ 50 years undergoing an initial screening colonoscopy in Calgary, Alberta, Canada. Associations between grams per day of total, processed, and unprocessed red meat from diet history questionnaires and ACRAs were evaluated with multivariable logistic regression models. We also applied cubic spline models fitted with three knots (10th, 50th, and 90th percentiles) to identify potential nonlinear associations. We did not observe a meaningful association between unprocessed red meat intake and the presence of ACRAs. In contrast, for every 10 g/d increase in total and processed meat intake, we observed an increase in the odds of ACRAs at the screening colonoscopy (adjusted odds ratio (OR) = 1.05, 95% [CI = 1.01-1.09], p = 0.04) and (adjusted OR = 1.11, 95% [CI = 1.02-1.20], p = 0.02), respectively. This study highlights the importance of differentiating between types of red meat consumption in the context of dietary risks associated with ACRAs.

Differences in circulating lymphocyte subpopulations among patients with inflammatory polyps, colorectal adenomas and colorectal cancer.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) may develop from focal changes within benign or precancerous polyps. The immune system's failure to detect and eradicate tumor cells due to immune surveillance evasion, allows cancer to develop and spread. This study aims to analyze the differences in circulating lymphocyte subpopulations in patients with colorectal inflammatory polyps, colorectal adenomas and CRC. PATIENTS AND METHODS: We retrospectively reviewed patients from September 2016 to December 2019 at the Shaoxing Second Hospital. Using flow cytometry, the subset distribution and immunophenotype of T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells were investigated in peripheral blood mononuclear cell samples. The counts of lymphocytes were determined by white blood cell counts. RESULTS: In total, 518 patients were included in this study. The counts of lymphocytes, T cells and NK cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts and percentages of CD8+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts of CD4+ T cells were lower in patients with CRC than inflammatory polyps. The percentages of CD4+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were higher than controls, but lower in the CRC than inflammatory polyps, colorectal adenomas. The counts and percentages of B cells were lower in CRC patients than colorectal adenomas patients. In addition, the percentages of B cells were higher in patients with inflammatory polyps and colorectal adenomas than in controls. CONCLUSIONS: The decrease in counts of lymphocyte, T cells, CD8+ T cells and NK cells in patients may be related to the dysplasia of epithelial cells. Furthermore, the B cells and CD4+ T cells may be related to the malignant growth of the dysplastic epithelial cells.

Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial.

OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.

Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients.

BACKGROUND: Colibactin, a genotoxin produced by polyketide synthase harboring (pks+) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pks+Escherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas. Previous research showed that a recurrent APC splice variant perfectly fits SBS88. METHODS: In this study, we explore the presence of colibactin-associated signatures and fecal pks in an unexplained polyposis cohort. Somatic targeted Next-Generation Sequencing (NGS) was performed for 379 patients. Additionally, for a subset of 29 patients, metagenomics was performed on feces and mutational signature analyses using Whole-Genome Sequencing (WGS) on Formalin-Fixed Paraffin Embedded (FFPE) colorectal tissue blocks. RESULTS: NGS showed somatic APC variants fitting SBS88 or ID18 in at least one colorectal adenoma or carcinoma in 29% of patients. Fecal metagenomic analyses revealed enriched presence of pks genes in patients with somatic variants fitting colibactin-associated signatures compared to patients without variants fitting colibactin-associated signatures. Also, mutational signature analyses showed enrichment of SBS88 and ID18 in patients with variants fitting these signatures in NGS compared to patients without. CONCLUSIONS: These findings further support colibactins ability to mutagenize colorectal mucosa and contribute to the development of colorectal adenomas and carcinomas explaining a relevant part of patients with unexplained polyposis.

Analysis of the Current Status and Factors Influencing Compliance with Colonoscopic Monitoring After Endoscopic Surgery for Advanced Colorectal Adenoma.

Background: Advanced colorectal adenomas are at a risk of malignant transformation following endoscopic resection, and colonoscopic monitoring interval after polypectomy have been widely used. This study aims to investigate the prevailing state of compliance with postoperative colonoscopic surveillance among patients with advanced colorectal adenomas and its' influencing factors at Affiliated Hospital of Jiangnan University between November 2020 and April 2021. Methods: A retrospective analysis was conducted on patients who underwent endoscopic treatment for ACA at Affiliated Hospital of Jiangnan University from November 2020 to April 2021. Compliance with postoperative colonoscopic surveillance was assessed based on established guidelines. Factors such as sociodemographic features, medical histories, and health beliefs were analyzed to determine their influence on compliance. Univariate analysis, survival analysis, and multi-factor Cox regression analysis were used for statistical evaluation. Results: A total of 511 patients were included in the study. The compliance rate was found to be 43.2%. The univariate analysis indicated that factors such as gender, education level, work status, type of health insurance, place of residence, marital status, type of consultation, presence of gastrointestinal symptoms, number of polyps, and the maximum diameter of polyps significantly affected compliance. Multi-factor Cox regression analysis revealed that female gender, absence of gastrointestinal symptoms, outpatient endoscopic treatment, and solitary polyps were independent factors influencing compliance. Reasons for poor compliance included underestimating the severity of the disease, fear of colonoscopy, and procedural complexities. Conclusion: Patients with advanced colorectal adenomas had poor compliance with postoperative colonoscopy monitoring. Tailored health education programs should be designed, targeting women, outpatients undergoing endoscopic procedures, and patients with solitary polyps to enhance their compliance with colonoscopy monitoring.

Is Metformin Associated with a Lower Prevalence of Polyps, Adenomas, and Colorectal Carcinoma in Patients with Diabetes Mellitus?

PURPOSE: Recent studies suggested a protective role of metformin in the development of colorectal cancer (CRC) and its precursors. We aimed to investigate if metformin was associated with a lower prevalence and number of colorectal polyps in diabetic patients and also adenomas, high-risk adenomas, and CRC. METHODS: Retrospective study on adult patients with diabetes mellitus followed in our hospital with a total colonoscopy between 2015 and 2019, treated with either metformin for > 5 years or other antidiabetic agent (control group). We assessed the number, size, and histopathology examination of proliferative lesions detected on colonoscopy. RESULTS: We included 401 patients aged 69 ± 9 years, 57% males, divided into two groups: treated with metformin (n = 260) and without (n = 141). The number of polyps detected was significantly lower in patients under metformin (p = 0.014). There was a nonsignificant trend towards lower polyp detection rates in the metformin compared to the control group both in unadjusted analysis (50% vs 60%, p = 0.058) and multivariable adjusted analysis (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.43-1.09, p = 0.111). In the latter, we identified male gender (OR 2.24, 95%CI 1.44-3.49, p < 0.001), age (OR 1.35 for every 10 years, 95%CI 1.07-1.71, p = 0.012), glycated hemoglobin value (OR 1.20 for every 1% increase, 95%CI 1.06-1.37, p = 0.005), and hypertension (OR 1.76, 95%CI 1.01-3.08, p = 0.046) as factors associated with a higher prevalence of polyps. We saw no statistically significant differences regarding adenoma (p = 0.231), high-risk adenoma (p = 0.810), and CRC (p = 0.705) diagnoses between groups. CONCLUSION: In our study, metformin was associated with less colorectal polyps in diabetic patients compared to other treatment modalities. We observed a nonsignificant trend towards lower polyp detection rates in the metformin group both in unadjusted and adjusted analyses.

Comparison of adenoma miss rate and adenoma detection rate between conventional colonoscopy and colonoscopy with second generation distal attachment cuff: a multicenter, randomized, back-to-back trial.

BACKGROUND AND AIMS: Endocuff VisionTM has been designed to enhance mucosal visualization thereby improving detection of (pre-)malignant colorectal lesions. This multicenter, international, back-to-back, randomized colonoscopy trial compared adenoma detection rate (ADR) and adenoma miss rate (AMR) between Endocuff Vision-assisted colonoscopy (EVC) and conventional colonoscopy (CC). METHODS: Patients aged 40-75 years referred for non-immunochemical fecal occult blood test-based screening, surveillance, or diagnostic colonoscopy were included at ten hospitals and randomized into four groups: Group 1; 2xCC, Group 2; CC followed by EVC, Group 3; EVC followed CC and Group 4; 2xEVC. Primary outcomes included ADR and AMR. RESULTS: A total of 717 patients were randomized of which 661 patients (92.2%) had one and 646 (90.1%) patients had two completed back-to-back colonoscopies. EVC did not significantly improve ADR compared to CC (41.1% [95%-CI;36.1-46.3] versus 35.5% [95%-CI;30.7-40.6], respectively, P=0.125), but EVC did reduced AMR by 11.7% (29.6% [95%-CI;23.6-36.5] versus 17.9% [95%-CI;12.5-23.5], respectively, P=0.049). AMR of 2xCC compared to 2xEVC was also not significantly different (25.9% [95%-CI;19.3-33.9] versus 18.8% [95%-CI;13.9-24.8], respectively, P=0.172). Only 3.7% of the polyps missed during the first procedures had advanced pathologic features. Factors affecting risk of missing adenomas were age (P=0.002), Boston Bowel Preparation Scale (P=0.008) and region where colonoscopy was performed (P<0.001). CONCLUSIONS: Our trial shows that EVC reduces the risk of missing adenomas but does not lead to a significant improved ADR. Remarkably, 25% of adenomas are still missed during conventional colonoscopies, which is not different from miss rates reported 25 years ago; reassuringly, advanced features were only found in 3.7% of these missed lesions. TRAIL REGISTRATION NUMBER: NCT03418948.

Association of tea and its extracts with colorectal adenomas: meta-analysis and systematic review.

Background: There are many studies on the association of tea and its extracts with colorectal adenomas, but the results have varied. The study aims to investigate the effect of tea and its extracts on colorectal adenomas using meta analysis and systematic review. Methods: Literature was obtained through PubMed, Cochrane Library, Embase and Chinese BioMedical Literature Service System since the establishment of the database until April 31, 2023. Search terms include adenomas, polyps, colorectal, rectal, rectum, tea, epigallocatechin, drinking and beverages. Meta-regression analysis was used to infer the source of heterogeneity. Heterogeneity was assessed using I2 statistics and Q test. The effect measures were odds ratio (OR) and 95% confidence interval (95% CI). Stata17.0 software was used for data processing. Results: The findings indicated that study design (t = 0.78, P = 0.454), types of tea intake (t = 1.35, P = 0.205), occurrences (t = -0.19, P = 0.852), regions (t = 1.13, P = 0.281) and grades of adenomas (t = 0.06, P = 0.952) were statistical homogeneity. Tea and its extracts were negatively correlated with the risk of colorectal adenomas (OR = 0.81, 95% CI: 0.66-0.98). No publication bias was found in this study (t = -0.22, P = 0.828) and the results are robust. Conclusion: This study suggests that tea and its extracts have a certain protective effect on colorectal adenomas, which provides scientific evidence for preventive strategies for colorectal adenomas. As for the causal relationship between tea and its extracts on colorectal adenomas, further prospective studies are needed.

Advancing Colorectal Cancer Screening: A Comprehensive Systematic Review of Artificial Intelligence (AI)-Assisted Versus Routine Colonoscopy.

Colorectal cancer (CRC) is a rapidly escalating public health concern, which underlines the significance of its early detection and the need for the refinement of current screening methods. In this systematic review, we aimed to analyze the potential advantages and limitations of artificial intelligence (AI)-based computer-aided detection (CADe) systems as compared to routine colonoscopy. This review begins by shedding light on the global prevalence and mortality rates of CRC, highlighting the urgent need for effective screening techniques and early detection of this cancer type. It addresses the problems associated with undetected adenomas and polyps and the subsequent risk of interval CRC following colonoscopy. The incorporation of AI into diagnostics has been studied, specifically the use of CADe systems which are powered by deep learning. The review summarizes the findings from 13 randomized controlled trials (RCTs) (2019-2023), evaluating the impact of CADe on polyp and adenoma detection. The findings from the studies consistently show that CADe is superior to conventional colonoscopy procedures in terms of adenoma detection rate (ADR) and polyp detection rate (PDR), particularly with regard to small and flat lesions which are easily overlooked. The review acknowledges certain limitations of the included studies, such as potential performance bias and geographic limitations. The review ultimately concludes that AI-assisted colonoscopy can reduce missed lesion rates and improve CRC diagnosis. Collaboration between experts and clinicians is key for successful implementation. In summary, this review analyzes recent RCTs on AI-assisted colonoscopy for polyp and adenoma detection. It describes the likely benefits, limitations, and future implications of AI in enhancing colonoscopy procedures and lowering the incidence of CRC. More double-blinded trials and studies among diverse populations from different countries must be conducted to substantiate and expand upon the findings of this review.

Association of clinical characteristics and recurrence of conventional colorectal adenomas with patient age: a single-center study.

OBJECTIVES: We performed a clinical study comparing early-onset and late-onset conventional colorectal adenomas (CCRAs) since little is known about the differences in their characteristics. METHODS: Pearson's chi-square test and the Kruskal‒Wallis test were used to compare basic information. MCAR tests and multiple imputation were performed to complete missing values. Multivariate logistic analysis and propensity score matching were used to identify the risk factors for recurrence. RESULTS: We included 2793 patients (688 with early-onset CCRAs and 2105 with late-onset CCRAs) from January 2017 to December 2021. Patients with early-onset CCRAs had higher levels of Hb, ALB, and triglycerides but lower HDL levels and N/L ratios. Moreover, we found that more early-onset CCRAs were in the left colon than late-onset CCRAs, and the size of early-onset CCRAs was larger. Early-onset CCRAs tended to lack pedicles compared to late-onset CCRAs. Additionally, the ratio of EMR and APC in early-onset CCRAs was higher than that in late-onset CCRAs, and the ratio of ESD and surgery for late-onset CCRAs was higher. We found that age ≥ 50 years, abnormal vessels, drinking alcohol, and DB and ALB levels may be risk factors for recurrence, while the LDL level may be a protective factor. Finally, analysis of cumulative recurrence rates after PSM showed that patients with late-onset CCRAs exhibited higher recurrence rates (P < 0.05). CONCLUSION: Compared with late-onset CCRAs, early-onset CCRAs were associated with higher triglyceride levels, lower HDL levels, and larger tumor volumes. Age ≥ 50 years, abnormal vessels, alcohol consumption, and DB and ALB levels were independent risk factors for recurrence of CCRAs.

Berberine: An inspiring resource for the treatment of colorectal diseases.

Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.

MALAT1 in Liquid Biopsy: The Diagnostic and Prognostic Promise for Colorectal Cancer and Adenomas?

Introduction: The development of colorectal cancer (CRC) is a multistep process accompanied by the accumulation of mutations that start from specific precancerous lesion - colorectal adenomas (CA). CRC incidence and mortality can be reduced by the early identification of these neoplasm. Colonoscopy is the most widely used screening method for CRC identification. Nowadays, clinical research interest is shifting to the use of liquid biopsy that may help with the early diagnosis of CA and CRC. In our previous study, we identified long non-coding RNA MALAT1 gene amplification associated with the development of CA. Methods: This study aimed to describe the potential of MALAT1 expression levels in the adenoma tissue of patients used in the previous study by real-time qPCR. Furthermore, we analysed the plasma samples of an independent group of patients with CA (n=97), CRC (n=101), and cancer-free individuals (CFI, n=48). Results: There was no difference in the MALAT1 expression level between CA patients with or without MALAT1 amplification. However, the plasma MALAT1 expression levels were significantly upregulated in patients with CRC and CA compared to CFI (for both p<0.001). Moreover, a correlation between MALAT1 expression and histological types of adenomas was identified- high-CRC-risk adenomas also displayed the highest MALAT1 expression levels. Furthermore, in CRC patients, MALAT1 levels were associated with a response to therapy. Conclusion: MALAT1 expression levels could serve as a promising circulating biomarker for early CA and CRC diagnosis, and even as a predictor of therapy response in CRC patients.

Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients.

Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.

Quality in colonoscopy: time to ensure national standards are implemented?

Background: High-quality colonoscopy is crucial to ensure complete mucosal visualisation and to maximise detection of pathology. Previous audits showing variable quality have prompted national and international colonoscopy improvement programmes, including the development of quality assurance standards and key performance indicators (KPIs). The most widely used marker of mucosal visualisation is the adenoma detection rate (ADR), however, histological confirmation is required to calculate this. We explored the relationship between core colonoscopy KPIs. Methods: Data were collected from colonoscopists in eight hospitals in North East England over a 6-month period, as part of a quality improvement study. Procedural information was collected including number of colonoscopies, caecal intubation rate (CIR), ADR and polyp detection rate (PDR). Associations between KPIs and colonoscopy performance were analysed. Results: 9265 colonoscopies performed by 118 endoscopists were included. Mean ADR and PDR per endoscopist were 16.6% (range 0-36.3, SD 7.4) and 27.2% (range 0-57.5, SD 9.3), respectively. Mean number of colonoscopies conducted in 6 months was 78.5 (range 4-334, SD 61). Mean CIR was 91.2% (range 55.5-100, SD 6.6). Total number of colonoscopies and ADR>15% were significantly associated (p=0.04). Undertaking fewer colonoscopies and using hyoscine butylbromide less frequently was significantly associated with ADR<15%. CIR, endoscopist grade, % male patients, mean patient age and CIR were not significantly related to ADR<15%. In adjusted analyses, factors which affected ADR were PDR and mean patient age. Conclusion: Colonoscopists who perform fewer than the nationally stipulated minimum of 100 procedures per year had significantly lower ADRs. This study demonstrates that PDR can be used as a marker of ADR; providing age is also considered.

Treatment of adenoma recurrence after endoscopic mucosal resection.

OBJECTIVE: Residual or recurrent adenoma (RRA) after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) of ≥20 mm is a major limitation. Data on outcomes of the endoscopic treatment of recurrence are scarce, and no evidence-based standard exists. We investigated the efficacy of endoscopic retreatment over time in a large prospective cohort. DESIGN: Over 139 months, detailed morphological and histological data on consecutive RRA detected after EMR for single LNPCPs at one tertiary endoscopy centre were prospectively recorded during structured surveillance colonoscopy. Endoscopic retreatment was performed on cases with evidence of RRA and was performed predominantly using hot snare resection, cold avulsion forceps with adjuvant snare tip soft coagulation or a combination of the two. RESULTS: 213 (14.6%) patients had RRA (168 (78.9%) at first surveillance and 45 (21.1%) thereafter). RRA was commonly 2.5-5.0 mm (48.0%) and unifocal (78.7%). Of 202 (94.8%) cases which had macroscopic evidence of RRA, 194 (96.0%) underwent successful endoscopic therapy and 161 (83.4%) had a subsequent follow-up colonoscopy. Of the latter, endoscopic therapy of recurrence was successful in 149 (92.5%) of 161 in the per-protocol analysis, and 149 (73.8%) of 202 in the intention-to-treat analysis, with a mean of 1.15 (SD 0.36) retreatment sessions. No adverse events were directly attributable to endoscopic therapy. Further RRA after endoscopic therapy was endoscopically treatable in most cases. Overall, only 9 (4.2%, 95% CI 2.2% to 7.8%) of 213 patients with RRA required surgery.Thus 159 (98.8%, 95% CI 95.1% to 99.8%) of 161 cases with initially successful endoscopic treatment of RRA and follow-up remained surgery-free for a median of 13 months (IQR 25.0) of follow-up. CONCLUSIONS: RRA after EMR of LNPCPs can be effectively treated using simple endoscopic techniques with long-term adenoma remission of >90%; only 16% required retreatment. Therefore, more technically complex, morbid and resource-intensive endoscopic or surgical techniques are required only in selected cases. TRIAL REGISTRATION NUMBERS: NCT01368289 and NCT02000141.