Colorectal cancer cell dormancy:An insight into pathways

Cancer cell dormancy(CCD)in colorectal cancer(CRC)poses a significant challenge to effective treatment.In CRC,CCD contributes to tumour recurrence,drug resistance,and amplifying the disease's burden.The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored.Therefore,understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies.This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD,emphasizing the roles of Hippo/YAP,pluripotent transcription factors such as NANOG,HIF-1αsignalling,and Notch signalling pathways.Additionally,ERK/p38α/β/MAPK pathways,AKT signalling pathway,and Extracellular Matrix Metalloproteinase Inducer,along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling,are also involved in promoting colorectal CCD.Highlighting their clinical significance,these findings may offer the potential for identifying key dormancy regulator pathways,improving treatment strategies,surmounting drug resistance,and advancing personalized medicine approaches.Moreover,insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles.It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several countries.AIM To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.METHODS This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies.Colonoscopy-related complications by age group were also determined.RESULTS The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age group.During the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age.Since 2009,the increase has been rapid,showing a pattern similar to the increase in colonoscopies.The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007.The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.CONCLUSION The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed.As the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

Has the open surgical approach in colorectal cancer really become uncommon?

Colorectal cancer is the third most common cancer in the world.Surgery is man-datory to treat patients with colorectal cancer.Can colorectal cancer be treated in laparoscopy?Scientific literature has validated the oncological quality of laparo-scopic approach for the treatment of patients with colorectal cancer.Randomized non-inferiority trials with good remote control have answered positively to this long-debated question.Early as 1994,first publications demonstrated technical feasibility and compliance with oncological imperatives and,as far as short-term outcomes are concerned,there is no difference in terms of mortality and post-operative morbidity between open and minimally invasive surgical approaches,but only longer operating times at the beginning of the experience.Subsequently,from 2007 onwards,long-term results were published that demonstrated the ab-sence of a significant difference regarding overall survival,disease-free survival,quality of life,local and distant recurrence rates between open and minimally in-vasive surgery.In this editorial,we aim to summarize the clinical and technical aspects which,even today,make the use of open surgery relevant and necessary in the treatment of patients with colorectal cancer.

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older people.Surgical management,despite advancements,requires careful consideration of preoperative patient status for optimal outcomes.AIM To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery.METHODS A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis.Only studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were included.Pooled effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were included.Compared with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow up.Frail patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control group.The risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail patients.CONCLUSION Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased mortality.Integrating frailty assessment appears crucial for tailored surgical management.

Association between triglyceride-glucose index and colorectal polyps:A retrospective cross-sectional study

BACKGROUND Colorectal polyps(CPs)are frequently occurring abnormal growths in the colorectum,and are a primary precursor of colorectal cancer(CRC).The triglyceride-glucose(TyG)index is a novel marker that assesses metabolic health and insulin resistance,and has been linked to gastrointestinal cancers.AIM To investigate the potential association between the TyG index and CPs,as the relation between them has not been documented.METHODS A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan,Jiangsu Province,China,between January 2020 and December 2022 were included in this retrospective cross-sectional study.After excluding individuals who did not meet the eligibility criteria,descriptive statistics were used to compare characteristics between patients with and without CPs.Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs.The TyG index was calculated using the following formula:Ln[triglyceride(mg/dL)×glucose(mg/dL)/2].The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports.RESULTS A nonlinear relation between the TyG index and the prevalence of CPs was identified,and exhibited a curvilinear pattern with a cut-off point of 2.31.A significant association was observed before the turning point,with an odds ratio(95% confidence interval)of 1.70(1.40,2.06),P<0.0001.However,the association between the TyG index and CPs was not significant after the cut-off point,with an odds ratio(95% confidence interval)of 0.57(0.27,1.23),P=0.1521.CONCLUSION Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals,suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps

BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled mucosa)surrounding colo-rectal polyps,caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors.CSM-positive colorectal polyps are associated with various diseases;however,their prognosis varies greatly.Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps.Improved imaging is required to diagnose and treat CSM-positive colorectal polyps.METHODS This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy.All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system.Based on the pathological results,patients were classified as non-neoplastic polyps(five juvenile polyps),neoplastic polyps,non-invasive high-grade neoplasia(NHGN),or submucosal invasive carcinoma(SM stage cancer).We analyzed and compared the clinical features,suspected risk factors for malignant transformation of neoplastic polyps,and early infiltration of sub-mucosal carcinoma.RESULTS The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps.Most NHGN polyps had a deeper red mucosal color.On logistic regression analyses,diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps.Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM;type 2 CSM was more common in neoplastic polyps.Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer.Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months.No tumor recurrence was found during either partial or complete endoscopic resection of the CSM.CONCLUSION CSM-positive colorectal polyps>1 cm in diameter or with deeper red mucosa may be related to NHGN.Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.

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.

Effect of colorectal cancer stem cells on the development and metastasis of colorectal cancer

The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients

BACKGROUND Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus(DM),posing a significant risk for colorectal cancer.Metformin,a widely prescribed biguanidine drug for type 2 DM,has been suggested to have potential chemoprophylactic effects against various cancers.AIM To explore the correlation between colorectal polyps and metformin use in type 2 DM patients.METHODS Type 2 DM patients were categorized into polyp and non-polyp groups.Following this,all patients were categorized into the type 2 DM-metformin,type 2 DM-non-metformin,and non-type 2 DM groups.Based on the baseline colonoscopy results,we performed pairwise comparisons of the incidence of colorectal polyps among the three groups.Additionally,we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use.Simultaneously,we focused on the specific pathological types of polyps and analyzed their relationship with metformin use.Finally,we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results.RESULTS The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps[odds ratio(OR)=0.502,95%confidence interval(CI):0.365-0.689;P<0.001].The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups(P>0.05).Furthermore,the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant(P>0.05).Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy(P>0.05).CONCLUSION Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation,independent of the hypoglycemic effect of metformin.

Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer

Helicobacter pylori(H.pylori)plays an important role in the development of gastric cancer,although its association to colorectal polyp(CP)or colorectal cancer(CRC)is unknown.In this issue of World Journal of Gastrointestinal Surgery,Zhang et al investigated the risk factors for H.pylori infection after colon polyp resection.Importantly,the researchers used R software to create a prediction model for H.pylori infection based on their findings.This editorial gives an overview of the association between H.pylori and CP/CRC,including the clinical significance of H.pylori as an independent risk factor for CP/CRC,the underlying processes of H.pylori-associated carcinogenesis,and the possible risk factors and identification of H.pylori.

Study on the Correlation between Metabolic Syndrome and Colorectal

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.

Artificial intelligence for characterization of diminutive colorectal polyps:A feasibility study comparing two computer-aided diagnosis systems

BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal polyps.AIM To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Polyps(AI4CRP)for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYE^(TM)(Fujifilm,Tokyo,Japan).CADx influence on the optical diagnosis of an expert endoscopist was also investigated.METHODS AI4CRP was developed in-house and CAD EYE was proprietary software provided by Fujifilm.Both CADxsystems exploit convolutional neural networks.Colorectal polyps were characterized as benign or premalignant and histopathology was used as gold standard.AI4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value(range 0.0-1.0).A predefined cut-off value of 0.6 was set with values<0.6 indicating benign and values≥0.6 indicating premalignant colorectal polyps.Low confidence characterizations were defined as values 40%around the cut-off value of 0.6(<0.36 and>0.76).Self-critical AI4CRP’s diagnostic performances excluded low confidence characterizations.RESULTS AI4CRP use was feasible and performed on 30 patients with 51 colorectal polyps.Self-critical AI4CRP,excluding 14 low confidence characterizations[27.5%(14/51)],had a diagnostic accuracy of 89.2%,sensitivity of 89.7%,and specificity of 87.5%,which was higher compared to AI4CRP.CAD EYE had a 83.7%diagnostic accuracy,74.2%sensitivity,and 100.0%specificity.Diagnostic performances of the endoscopist alone(before AI)increased nonsignificantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE(AI-assisted endoscopist).Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems,except for specificity for which CAD EYE performed best.CONCLUSION Real-time use of AI4CRP was feasible.Objective confidence values provided by a CADx is novel and self-critical AI4CRP showed higher diagnostic performances compared to AI4CRP.

Clinical Efficacy of Laparoscopic Radical Colorectal Cancer Treatment for Colorectal Cancer and Its Effect on Immune Function

Objective:To explore the therapeutic effect of laparoscopic radical colorectal cancer treatment in colorectal cancer patients.Methods:A total of 50 colorectal cancer patients treated between August 2018 and August 2023 were randomly divided into two groups:Group A underwent laparoscopic radical colorectal cancer surgery,while Group B received open surgery.Clinical indicators,inflammatory factors,immune function indicators,and complications were compared between the two groups.Results:Group A showed significantly shorter operation times,faster recovery times,and reduced hospital stays compared to Group B.Additionally,Group A had less abdominal drainage and intraoperative bleeding(P<0.05).Levels of interleukin(IL)-4,IL-6,ultrasensitive C-reactive protein(hs-CRP),and tumor necrosis factor-alpha(TNF-α)were lower in Group A compared to Group B(P<0.05).Furthermore,immune function indicators,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were better in Group A(P<0.05).The complication rate in Group A was also lower than in Group B(P<0.05).Conclusion:Laparoscopic radical treatment for colorectal cancer is efficient and feasible,causing minimal immune function impairment and inflammatory response.It also shortens postoperative recovery time.

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.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Colorectal cancer screening:A review of current knowledge and progress in research

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.