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 ...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.展开更多
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...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.展开更多
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,...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 “high-risk” adenomas), and rated each trial’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.展开更多
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 adenom...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.展开更多
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 s...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.展开更多
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-...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.展开更多
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 dia...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.展开更多
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 characteristi...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.展开更多
OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jian...OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jianpi formulas for CRA post-polypectomy were systematically retrieved from eight electronic databases.The quality of the methodology was assessed using the Cochrane collaboration tool.The Grades of Recommendations Assessment Development and Evaluation(GRADE)approach was employed for evidence assessment.Statistical analyses were conducted using Statistics and Data Analysis(STATA)17(StataCorp(College Station,TX,USA)and Review Manager(RevMan)5.4(The Cochrane Collaboration(London,UK).RESULTS:The Meta-analysis,encompassing 18 RCTs with 1838 patients,revealed that Jianpi formulas significantly outperformed postoperative routine treatment.It demonstrated a reduction in the half-year recurrence rate[relative risk(RR)=0.41,95%confidence interval(CI)=0.33-0.49,Z=9.08,P<0.00001],the oneyear recurrence rate[RR=0.58,95%CI=0.49-0.69,Z=6.12,P<0.00001],and an enhancement in the clinical effective rate[RR=1.27,95%CI=1.19-1.36,Z=7.06,P<0.00001].The half-year recurrence rate and the clinical effective rate were medium-quality evidence.The one-year recurrence rate was low-quality evidence.Additionally,Jianpi formulas appear to be safe and do not increase adverse reactions compared to postoperative routine treatment alone.CONCLUSION:Jianpi formulas exhibit efficacy in reducing postoperative half-year and one-year recurrence rates while improving the clinical effective rate after polypectomy for CRA.展开更多
Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: Th...Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.展开更多
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 ep...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.展开更多
BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence[e.g.,tubular adenoma(TA)]often progress to malignancy and are closely associated with changes in the composition of the gut mic...BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence[e.g.,tubular adenoma(TA)]often progress to malignancy and are closely associated with changes in the composition of the gut microbiome.There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway,such as hyperplastic polyps(HP).Exploration of microbiome alterations asso-ciated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis.AIM To investigate gut microbiome signatures,microbial associations,and microbial functions in HP and TA patients.METHODS Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps[control group(CT),n=40],patients with HP(n=52),and patients with TA(n=60).Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA.Analytical techniques in this study included differential abundance analysis,co-occurrence network analysis,and differential pathway analysis.RESULTS Colorectal cancer(CRC)-associated bacteria,including Streptococcus gallolyticus(S.gallolyticus),Bacteroides fragilis,and Clostridium symbiosum,were identified as characteristic microbial species in TA patients.Mediterraneibacter gnavus,associated with dysbiosis and gastrointestinal diseases,was significantly differentially abundant in the HP and TA groups.Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively,whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis(e.g.,mevalonate);S.gallolyticus was a major contributor.Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients,whereas TA patients exhibited co-occurrence of CRC-associated bacteria.Furthermore,the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients.CONCLUSION This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development,providing insights concerning the roles of microbial species,functional pathways,and microbial interactions in colorectal carcinogenesis.展开更多
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)scre...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.展开更多
Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences ...Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences colorectal adenoma encompass chronic inflammation, insulin resistance, oxidative stress, and dysbiosis of the intestinal flora. This review aims to consolidate the understanding of the association between metabolic syndrome and colorectal adenoma, elucidating the interconnected mechanisms between different metabolic syndrome-related disorders and colorectal adenoma. By shedding light on these connections, this review offers valuable insights for the preventive strategies targeting colorectal adenoma.展开更多
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 earl...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.展开更多
BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in var...BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression.Although Numb,Itch,and seven in absentia homolog-1(Siah-1)have been shown to contribute to the regulation of Notch signaling,their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.AIM To evaluate Numb,Itch,and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.METHODS Expression of Notch-1,Numb,Itch,and Siah-1 was investigated in 50 colorectal carcinomas,30 adenomas,and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(PCR)analyses.RESULTS In contrast to Notch-1,which is expressed at higher levels in tumor tissues and adenomas,expression of Numb,Itch,and Siah-1 was stronger and more frequent in normal mucosa(P<0.01).There was a positive correlation between Notch-1 expression and high histological grade,the presence of lymph node metastasis,and advanced-stage tumors,whereas expression of Numb,Itch,and Siah-1 was absent or reduced in tumors with these clinicopathological parameters(P<0.05).In survival analysis,expression of Notch was related to poor prognosis but that of Numb,Itch,and Siah-1 correlated with improved survival(P<0.05).Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis(P<0.05).CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb,Itch,and Siah-1 expression is associated with carcinogenesis.Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma(CRC)progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.展开更多
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 h...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.展开更多
Objective:To investigate the efficacy of Buyang Huanwu Decoction in preventing the recurrence of advanced colonic adenomatous polyps after surgery.Methods:A total of 160 patients who underwent endoscopic treatment for...Objective:To investigate the efficacy of Buyang Huanwu Decoction in preventing the recurrence of advanced colonic adenomatous polyps after surgery.Methods:A total of 160 patients who underwent endoscopic treatment for advanced adenomatous polyps of the large intestine at the First People’s Hospital of Jintan,Changzhou,between March 2022 and March 2024 were enrolled in this study.The patients were randomly divided into an intervention group and a control group using a random number table.The control group received routine postoperative care,while the intervention group received Buyang Huanwu Decoction,starting one month after surgery.The decoction was administered warm,twice daily(200 ml per dose),one dose per day,for a total treatment duration of three months.Results:Before the intervention,there were no significant differences between the two groups in terms of TCM syndrome scores,and serum levels of G-17,IL-18,IL-6,COX2,and CRP(P>0.05).After the intervention,both groups showed a decrease in TCM syndrome scores and serum levels of G-17,IL-18,IL-6,COX2,and CRP compared to pre-intervention values.The intervention group demonstrated a significantly greater reduction(P<0.05).Three months after the intervention,there was no significant difference in polyp recurrence rates between the two groups(P>0.05).However,six and twelve months after the intervention,the recurrence rates in the intervention group were significantly lower than those in the control group(P<0.05).The incidence of adverse reactions was compared between two groups of patients.The intervention group had an incidence of 12.5%,while the control group had an incidence of 6.25%,with no statistically significant difference(P>0.05).Conclusion:Buyang Huanwu Decoction has significant efficacy in preventing the recurrence of advanced colonic adenomatous polyps after surgery.It improves TCM syndrome scores,reduces oncogenic and inflammatory factors,significantly lowers postoperative polyp recurrence rates,and demonstrates good safety.It is a promising treatment for clinical promotion and application.展开更多
AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cy...AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.展开更多
Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic al...Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.展开更多
文摘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.
文摘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.
文摘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 “high-risk” adenomas), and rated each trial’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.
文摘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.
基金Supported by the Public Health Service grants, No. R01CA-51932 to RMB (National Cancer Institute)Center for Colon Cancer Research grant, No. RR017698 to FGB from National Institutes of Health, Department of Health and Human Services
文摘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.
基金Supported by Grant-in-Aid for Research from the Third-Term Comprehensive Control Research for Cancer Center of the Ministry of Health, Labor and Welfare, JapanGrant from the Ministry of Education, Culture, Sports, Science and Technology, Japan(KIBAN-B)the "Collaborative Development of Innovative Seeds" Grant Program from the Japan Science and Technology Agency
文摘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.
基金Supported by a grant from the ELAN-Program of the FAUErlangen, Germany, No. 00.05.31.1
文摘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.
基金Supported by the National Natural Science Foundation of China,No.62375202Natural Science Foundation of Tianjin,No.23JCYBJC00950+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,No.TJWJ2022XK034Research Project in Key Areas of Traditional Chinese Medicine in 2024,No.2024022.
文摘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.
基金Jinhua Traditional Chinese Medicine Science and Technology Research Project:Gut Microbiota Distribution Characteristics in Spleen-Deficiency Colorectal Adenoma Patients(No.2023KR04)Jinhua Traditional Chinese Medicine Science and Technology Major Research Project:Clinical Efficacy and Mechanism of Shugan Jianpi Tiaochang Pills in Preventing Postoperative Recurrence of Colorectal Adenomas based on Metabolomics Technology(No.2024ZD03)。
文摘OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jianpi formulas for CRA post-polypectomy were systematically retrieved from eight electronic databases.The quality of the methodology was assessed using the Cochrane collaboration tool.The Grades of Recommendations Assessment Development and Evaluation(GRADE)approach was employed for evidence assessment.Statistical analyses were conducted using Statistics and Data Analysis(STATA)17(StataCorp(College Station,TX,USA)and Review Manager(RevMan)5.4(The Cochrane Collaboration(London,UK).RESULTS:The Meta-analysis,encompassing 18 RCTs with 1838 patients,revealed that Jianpi formulas significantly outperformed postoperative routine treatment.It demonstrated a reduction in the half-year recurrence rate[relative risk(RR)=0.41,95%confidence interval(CI)=0.33-0.49,Z=9.08,P<0.00001],the oneyear recurrence rate[RR=0.58,95%CI=0.49-0.69,Z=6.12,P<0.00001],and an enhancement in the clinical effective rate[RR=1.27,95%CI=1.19-1.36,Z=7.06,P<0.00001].The half-year recurrence rate and the clinical effective rate were medium-quality evidence.The one-year recurrence rate was low-quality evidence.Additionally,Jianpi formulas appear to be safe and do not increase adverse reactions compared to postoperative routine treatment alone.CONCLUSION:Jianpi formulas exhibit efficacy in reducing postoperative half-year and one-year recurrence rates while improving the clinical effective rate after polypectomy for CRA.
文摘Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.
基金The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
文摘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.
基金Supported by Chulabhorn Royal Academy(Fundamental Fund:Fiscal year 2022 by National Science Research and Innovation Fund),No.FRB650039/0240 Project Code 165422.
文摘BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence[e.g.,tubular adenoma(TA)]often progress to malignancy and are closely associated with changes in the composition of the gut microbiome.There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway,such as hyperplastic polyps(HP).Exploration of microbiome alterations asso-ciated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis.AIM To investigate gut microbiome signatures,microbial associations,and microbial functions in HP and TA patients.METHODS Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps[control group(CT),n=40],patients with HP(n=52),and patients with TA(n=60).Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA.Analytical techniques in this study included differential abundance analysis,co-occurrence network analysis,and differential pathway analysis.RESULTS Colorectal cancer(CRC)-associated bacteria,including Streptococcus gallolyticus(S.gallolyticus),Bacteroides fragilis,and Clostridium symbiosum,were identified as characteristic microbial species in TA patients.Mediterraneibacter gnavus,associated with dysbiosis and gastrointestinal diseases,was significantly differentially abundant in the HP and TA groups.Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively,whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis(e.g.,mevalonate);S.gallolyticus was a major contributor.Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients,whereas TA patients exhibited co-occurrence of CRC-associated bacteria.Furthermore,the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients.CONCLUSION This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development,providing insights concerning the roles of microbial species,functional pathways,and microbial interactions in colorectal carcinogenesis.
基金This study was approved by the Institutional Review Board(IRB number:18CR-31902-01)of the Lundquist Institute at Harbor-UCLA.
文摘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.
文摘Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences colorectal adenoma encompass chronic inflammation, insulin resistance, oxidative stress, and dysbiosis of the intestinal flora. This review aims to consolidate the understanding of the association between metabolic syndrome and colorectal adenoma, elucidating the interconnected mechanisms between different metabolic syndrome-related disorders and colorectal adenoma. By shedding light on these connections, this review offers valuable insights for the preventive strategies targeting colorectal adenoma.
文摘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.
基金Akdeniz University Scientific Research Foundation,Turkey,No.2017040103020.
文摘BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression.Although Numb,Itch,and seven in absentia homolog-1(Siah-1)have been shown to contribute to the regulation of Notch signaling,their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.AIM To evaluate Numb,Itch,and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.METHODS Expression of Notch-1,Numb,Itch,and Siah-1 was investigated in 50 colorectal carcinomas,30 adenomas,and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(PCR)analyses.RESULTS In contrast to Notch-1,which is expressed at higher levels in tumor tissues and adenomas,expression of Numb,Itch,and Siah-1 was stronger and more frequent in normal mucosa(P<0.01).There was a positive correlation between Notch-1 expression and high histological grade,the presence of lymph node metastasis,and advanced-stage tumors,whereas expression of Numb,Itch,and Siah-1 was absent or reduced in tumors with these clinicopathological parameters(P<0.05).In survival analysis,expression of Notch was related to poor prognosis but that of Numb,Itch,and Siah-1 correlated with improved survival(P<0.05).Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis(P<0.05).CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb,Itch,and Siah-1 expression is associated with carcinogenesis.Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma(CRC)progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.
基金Supported in part by Natural Science Foundation of Hubei Province (No. 302-131703)
文摘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.
基金Special research and development project of the off-campus teaching base of Jiangsu Medical Vocational College(Project No.:20229121)National Famous and Old Chinese Medicine Doctors’Inheritance Studio Construction Project of the National Administration of Traditional Chinese Medicine(Project No.:SATCM Human Education Development[2011]No.41)The Third National Medical Master Inheritance Studio and National Famous Chinese Medicine Doctors’Inheritance Studio Construction Project of the National Administration of Traditional Chinese Medicine(Project No.:SATCM Human Education Office Letter[2018]No.119)。
文摘Objective:To investigate the efficacy of Buyang Huanwu Decoction in preventing the recurrence of advanced colonic adenomatous polyps after surgery.Methods:A total of 160 patients who underwent endoscopic treatment for advanced adenomatous polyps of the large intestine at the First People’s Hospital of Jintan,Changzhou,between March 2022 and March 2024 were enrolled in this study.The patients were randomly divided into an intervention group and a control group using a random number table.The control group received routine postoperative care,while the intervention group received Buyang Huanwu Decoction,starting one month after surgery.The decoction was administered warm,twice daily(200 ml per dose),one dose per day,for a total treatment duration of three months.Results:Before the intervention,there were no significant differences between the two groups in terms of TCM syndrome scores,and serum levels of G-17,IL-18,IL-6,COX2,and CRP(P>0.05).After the intervention,both groups showed a decrease in TCM syndrome scores and serum levels of G-17,IL-18,IL-6,COX2,and CRP compared to pre-intervention values.The intervention group demonstrated a significantly greater reduction(P<0.05).Three months after the intervention,there was no significant difference in polyp recurrence rates between the two groups(P>0.05).However,six and twelve months after the intervention,the recurrence rates in the intervention group were significantly lower than those in the control group(P<0.05).The incidence of adverse reactions was compared between two groups of patients.The intervention group had an incidence of 12.5%,while the control group had an incidence of 6.25%,with no statistically significant difference(P>0.05).Conclusion:Buyang Huanwu Decoction has significant efficacy in preventing the recurrence of advanced colonic adenomatous polyps after surgery.It improves TCM syndrome scores,reduces oncogenic and inflammatory factors,significantly lowers postoperative polyp recurrence rates,and demonstrates good safety.It is a promising treatment for clinical promotion and application.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2012/15036-8National Council for Scientific and Technological Development(CNPq),No.474.776/2013-1+2 种基金the Sao Paulo Research Foundation(FAPESP,NO.2015/21464-0)for the support for English revisionthe Coordination for the Improvement of Higher Education Personnel(CAPES)for the doctoral scholarshipthe National Council for Scientific and Technological Development(CNPq,NO.310120/2015-2)for the productivity research scholarship
文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.
文摘Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.
