Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Long-term impact of artificial intelligence on colorectal adenoma detection in high-risk colonoscopy

BACKGROUND Improved adenoma detection rate(ADR)has been demonstrated with artificial intelligence(AI)-assisted colonoscopy.However,data on the real-world appli-cation of AI and its effect on colorectal cancer(CRC)screening outcomes is limited.AIM To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or sympt-oms.METHODS AI software(GI Genius,Medtronic)was implemented into the standard proced-ure protocol in November 2022.Data was collected on patient demographics,procedure indication,polyp size,location,and pathology.CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up.RESULTS We evaluated 1008 colonoscopies(278 pre-AI,255 early post-AI,285 established post-AI,and 190 late post-AI).The ADR was 38.1%pre-AI,42.0%early post-AI(P=0.77),40.0%established post-AI(P=0.44),and 39.5%late post-AI(P=0.77).There were no significant differences in polyp detection rate(PDR,baseline 59.7%),advanced ADR(baseline 16.2%),and non-neoplastic PDR(baseline 30.0%)before and after AI introduction.CONCLUSION In patients with an increased pre-test probability of having an abnormal colonoscopy,the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy.Although the potential of AI in colonoscopy is undisputed,current AI technology may not universally elevate screening metrics across all situations and patient populations.Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.

Advancing Early Detection of Colorectal Adenomatous Polyps via Genetic Data Analysis: A Hybrid Machine Learning Approach

In this study, a hybrid machine learning (HML)-based approach, incorporating Genetic data analysis (GDA), is proposed to accurately identify the presence of adenomatous colorectal polyps (ACRP) which is a crucial early detector of colorectal cancer (CRC). The present study develops a classification ensemble model based on tuned hyperparameters. Surpassing accuracy percentages of early detection approaches used in previous studies, the current method exhibits exceptional performance in identifying ACRP and diagnosing CRC, overcoming limitations of CRC traditional methods that are based on error-prone manual examination. Particularly, the method demonstrates the following CRP identification accuracy data: 97.7 ± 1.1, precision: 94.3 ± 5, recall: 96.0 ± 3, F1-score: 95.7 ± 4, specificity: 97.3 ± 1.2, average AUC: 0.97.3 ± 0.02, and average p-value: 0.0425 ± 0.07. The findings underscore the potential of this method for early detection of ACRP as well as clinical use in the development of CRC treatment planning strategies. The advantages of this approach are highly expected to contribute to the prevention and reduction of CRC mortality.

Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

BACKGROUNDGhrelin is an adipokine that plays an important role in energy balance. Expressionof ghrelin and ghrelin receptor has been investigated in different tissues andtumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectaltumors are scarce and no data on expression of ghrelin and its receptor incolorectal adenomas has been published. Ghrelin and ghrelin receptor werehighly expressed in colon carcinoma cells while expression was decreased in lessdifferentiated tumors, presuming that ghrelin might be important in early phasesof tumorigenesis.AIMTo investigate the expression of ghrelin and ghrelin receptor in human colorectaladenomas and adjacent colorectal tissue.METHODSIn this prospective study (conducted from June 2015 until May 2019) we included92 patients (64 male and 28 female) who underwent polypectomy for colorectaladenomas in the Department of Gastroenterology and Hepatology, “Sestre milosrdnice” Clinical Hospital Center in Zagreb, Croatia. After endoscopicremoval of colorectal adenoma, an additional sample of colon mucosa in theproximity of the adenoma was collected for pathohistological analysis. Adenomaswere graded according to the stage of dysplasia, and ghrelin and ghrelin receptorexpression were determined immunohistochemically in both adenoma andadjacent colon tissue using the polyclonal antibody for ghrelin (ab150514,ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAMInc, Cambridge, United States). Categorical and nominal variables were describedthrough frequencies and proportions and the difference between specific groupswere analyzed with Fisher’s and Fisher-Freeman-Halton’s method respectively.Spearman's rank correlation coefficient was determined for correlation ofexpression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissuewith the grade of adenoma dysplasia.RESULTSAmong 92 patients with colorectal adenoma 43 had adenomas with high-gradedysplasia (46.7%). High expression of ghrelin was 7 times more common in highgradeadenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048),while the expression of ghrelin in adjacent colon tissue was low. We found nocorrelation between ghrelin receptor expression in adenoma and adjacent colontissue and the grade of colorectal adenoma dysplasia. The most significantcorrelation was found between ghrelin and ghrelin receptor expression inadenomas with high-grade dysplasia (rho = 0.519, P < 0.001).CONCLUSIONGhrelin and ghrelin receptor are expressed in colorectal adenoma and adjacenttissue with ghrelin expression being more pronounced in high grade dysplasia asa possible consequence of increased local synthesis.

Calcium supplementation for the prevention of colorectal adenomas: a systematic review and meta-analysis of randomized controlled trials

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or &#x0201c;high-risk&#x0201d; adenomas), and rated each trial&#x02019;s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.

Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies

To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODSPubMed and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios (ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTSA total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary (OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, Pheterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma (OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, Pheterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-α and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00 (95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19 (95%CI: 0.92-1.55).CONCLUSIONSummary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.

Measurement of biological age may help to assess the risk of colorectal adenoma in screening colonoscopy

AIM To investigate the clinical utility of biological age(BA) measurement in screening colonoscopy for the detection of colorectal adenomas in the average-risk population.METHODS A consecutive series of asymptomatic subjects aged ≥ 30 years who underwent colonoscopy in routine check-ups were enrolled. Colorectal adenoma was classified according to size, number, and location. BAs were calculated using the MEDIAGETM Biological Age Measurement System.RESULTS A total of 2696 subjects were investigated(1876 men and 820 women). The mean chronological age(CA) was 46.0 years and the mean BA was 44.7 years. Metabolic syndrome(MS) was diagnosed in 218 subjects(8.1%). The prevalence of overall colorectal adenoma was 23.1%(622/2,696). When the subjects were divided into four groups based on BA(≤ 39 years; 40-49 years; 50-59 years; ≥ 60 years), the prevalence of colorectal adenoma was increased as BA increased(P < 0.001). Colorectal adenoma located in the proximal colon was more prevalent in the BA-dominant group(BA-CA ≥ 5years) than the CA-dominant group(CA-BA ≥ 5 years)(P = 0.034). When the subjects were categorized into four groups according to MS and age gap between BA and CA, the incidence of colorectal adenoma increased with MS and BA-dominance(P < 0.05).CONCLUSION Measurement of BA may help to assess the risk of colorectal adenoma in screening colonoscopy.

Leptin and peroxisome proliferator-activated receptor γ expression in colorectal adenoma

AIM： To investigate the expressions of leptin and per- oxisome proliferator-activated receptor y （PPARG） in relation to body mass index （BMI）. METHODS： We evaluated leptin and PPARG expres- sion in 30 adenomas over 1 cm in size by immunohisto- chemical staining. In addition, clinicopathologic features including BMI were assessed. RESULTS： PPARG and leptin expression showed a strong positive correlation （P = 0.035）. The average BMI of the leptin-positive group was higher than that of the leptin-negative group （25.4 ＋ 3.4 kg/m2 vs 22.6 ＋ 2.4 kg/m2, P = 0.018）, and leptin expression was sig- nificantly correlated with high BMI （P = 0.024）. Leptinexpression was more frequently observed in intermedi- ate/high grade dysplasia than in low grade dysplasia （P = 0.030）. However, PPARG expression was not cor- related with BMI and grade of dysplasia. CONCLUSION： BMI has influenced on the leptin ex- pression of colorectal adenoma. The exact mechanism underlies the strong correlation between leptin and PPARG expression needs further study.

Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance

Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.

Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic colorectal adenomas

AIM： Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor （VDR）. The aim of this study was to investigate whether a novel G （allele ‘U’g〉A （allele ‘u’ polymorphism （Tru9I） in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study. METHODS： Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism. RESULTS： The frequencies of ‘U’ and ‘u’ alleles were 89.3% and 10.7%, respectively. The ‘Uu’ and ‘uu’ genotypes were associated with decreased risk for adenoma （OR, 0.71; 95%CI, 0.40-1.25）. The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile： the odds ratios （ORs） were, 0.51 （95%CI, 0.21-1.24）, 0.37 （95%CI, 0.11-1.28）, 0.68 （95%CI, 0.33- 1.41）, and 0.36 （95%CI, 0.13-0.97） respectively. In joint/ combined analyses, inverse associations were more obvious among those who had at least one ‘u’ allele and also were younger （OR, 0.60; 95%CI, 0.26-1.37）, women （OR, 0.38; 95%CI, 0.17-0.88）, did not smoke （OR, 0.39; 95%CI, 0.13-1.23）, or took NSAID （OR, 0.38; 95%CI, 0.12-1.25）, but no evidence existed for interactions with calcium or vitamin D intake.CONCLUSION： Our findings suggest that the VDR TrugI polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.

Texture and color enhancement imaging for detecting colorectal adenomas: Good, but not good enough

Texture and color enhancement imaging(TXI)has been developed as a novel image-enhancing endoscopy.However,the effectiveness of TXI detecting adenomas is inferior to narrow band imaging.Thus,future studies will need to focus on investigating the feasibility of such combination in clinical settings in order to provide patients with more accurate diagnoses.

Lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma

Objective:The aim of this study was to investigate lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma.Methods:Analyses were based on data from 100 subjects with histologically confirmed adenomas(cases) and 50 adenoma-free control subjects,all of whom had colonoscopy.The subjects were divided into two groups:those with no adenoma and those with adenoma.According to subsite of adenomas the subjects with adenoma were divided into group of distal adenoma and group of proximal adenoma.According to histology of adenomas the subjects with adenoma were divided into group of villiform adenoma and group of tubular + tubulo-villous adenoma.Among the groups,the serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),lowdensity lipoprotein cholesterol(LDL-C),and lipid peroxidation product malondialdehyde(MDA) were compared in all the patients.Results:Plasma total cholesterol and MDA level in group of adenomas were significantly higher than that in group of control subjects,but plasma HDL-C level was low in group of adenomas(P<0.05).Plasma total cholesterol and MDA levels were positively related to distal and villiform adenomas(P<0.05).Conclusion:The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas.

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

Prediction of the mechanism of berberine in the prevention and treatment of colorectal adenoma cancerizat based on network pharmacology and molecular docking technology

To predict the potential mechanism of prevention and treatment of colorectal adenoma canceration by berberine and the docking of main key targets by computer virtual method.Methods:The related targets of berberine,colorectal adenoma and colorectal cancer were collected in various databases;the key targets were obtained by intersection;the protein protein interaction network and 6 kinds of enrichment analysis of key potential targets were completed by corresponding databases;the main key targets and berberine molecules were obtained for molecular docking.Results:There were 319 unique targets for berberine,3,279 for intestinal adenoma and 4,119 for colorectal cancer.The protein protein interaction network of key target involved 66 proteins.In the results of Gene Ontology enrichment,28 items related to biological process,28 items related to cell composition,30 items related to molecular function,26 items related to Kyoto Encyclopedia of Genes and Genomes pathway enrichment,35 items related to TargetScan microRNA,15 items related to Human Phenotype Ontology.TP53 and CYCS are the 2 key targets involved in the system enrichment.After docking,berberine was closely bound to theα-helix and β-fold of TP53 protein,and to theα-helix of CYCS protein.Conclusion:The potential mechanism of berberine in the prevention and treatment of colorectal adenoma canceration may be related to the regulation of cell apoptosis,metabolic pathways and biological activities of various enzymes.berberine,as a small molecular ligand,has the characteristics of multi-target,multi-channel and multi-system mechanism.In the prediction results,berberine,as a small molecular ligand,can closely bind with the main key targets related to colorectal adenoma canceration.

Non-compliance in surveillance for patients with previous resection of large (≥ 1 cm) colorectal adenomas

AIM: To assess the extent and reasons of non- compliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fi fty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians. RESULTS: Fifty-four out of 158 patients (34.2%) neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%). In a multivariate analysis, the factors including female gender (P = 0.036) and age > 62 years (P = 0.016) proved to be signif icantly associated with non-compliance in surveillance. CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance. This applies particularly to women’s compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.

Phosphatase and tensin homology deleted in chromosome 10,hypoxia-inducible factor-1 alpha gene expression in colorectal adenoma and adenocarcinoma and their relation to vascular endothelial growth factor protein expression

To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.

Folic acid supplementation inhibits recurrence of colorectal adenomas:A randomized chemoprevention trial

AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.

Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram

BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.

The first year follow-up after colorectal adenoma polypectomyis important: A multiple-center study in symptomatichospital-based individuals in China

The recurrence of colorectal adenoma(CRA)is high.Although there are guidelines for colonoscopy surveillance after polypectomy in other countries,little is known about its recurrence rate and recurrence peak,especially in China.The aim of the present research is to investigate how long after polypectomy follow-up should take and to analyze risk factors of recurrence.1208 patients who received polypectomies fromfive clinical research centers in four regions of China(Shanghai,Guangzhou,Nanjing and Beijing)were included.They were divided into 4 groups:group A(follow-up≤1 year after poly-pectomy),group B(follow-up 2–3 years after polypect-omy),group C(follow-up 4–5 years after polypectomy),and group D(follow-up>5 years after polypectomy).The sex,age,adenoma location,size,number,and pathological characteristics were compared.On the whole,the recur-rence rate was 59.46%in group A,61.09%in group B,78.07%in group C,and 87.12%in group D,which indicated an increased tendency with a prolonged follow-up duration.There was a significant difference between group A and C or D,and between group B and C or D(P<0.01),but there was no statistical difference between group A and B.Additionally,the recurrent patients in thefirst year had a recurrence rate of 97.33%in thefirst three years(59.46/61.09),which means that the peak of recurrence was almost entirely concentrated in thefirst year.The recurrence rate was higher in males and the elder.The risk factors included multiple numbers,villous feature,high-grade dysplasia of medium or smaller size and location in the distal colon.In conclusion,the peak of recurrence was almost totally concentrated in thefirst year;meanwhile,thefirst year follow-up is of critical importance in China.It may not be necessary to do the follow-up examination during the second and third years,but after three years,another colonoscopy should be undertaken.