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.

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.

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.

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.

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.

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.

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.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

Recent clinical trials and optical control as a potential strategy to develop microtubule-targeting drugs in colorectal cancer management

Colorectal cancer(CRC)has remained the second and the third leading cause of cancer-related death worldwide and in the United States,respectively.Although significant improvement in overall survival has been achieved,death in adult populations under the age of 55 appears to have increased in the past decades.Although new classes of therapeutic strategies such as immunotherapy have emerged,their application is very limited in CRC so far.Microtubule(MT)inhibitors such as taxanes,are not generally successful in CRC.There may be some way to make MT inhibitors work effectively in CRC.One potential advantage that we can take to treat CRC may be the combination of optical techniques coupled to an endoscope or other fiber optics-based devices.A combination of optical devices and photo-activatable drugs may allow us to locally target advanced CRC cells with highly potent MT-targeting drugs.In this Editorial review,we would like to discuss the potential of optogenetic approaches in CRC management.

Improving colorectal cancer screening programs

In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology.They suggest policies for more effective colorectal screening.Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening.Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps.However,colonoscopy is an invasive process,and fecal tests such as the current hemoglobin immunodetection were developed,followed by endoscopy,as the general tool for population screening,avoiding logistical and economic problems.Even so,participation and adherence rates are low.Different screening options are being developed with the idea that if people could choose between the ones that best suit them,participation in population-based screening programs would increase.Blood tests,such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA,showed a similar accuracy rate to stool tests for cancer,but were less sensitive for advanced precancerous lesions.At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer,novel immune system-related biomarkers and information on patients’immune parameters,such as cell counts of different immune populations,were studied for the early detection of colorectal cancer,since they could be effective in asymptomatic people,appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood.sCD26,for example,detected 80.37%of advanced adenomas.To reach as many eligible people as possible,starting at an earlier age than current programs,the direction could be to apply tests based on blood,urine or salivary fluid to samples taken during routine visits to the primary health system.

Application of exosomal miRNA mediated macrophage polarization in colorectal cancer:Current progress and challenges

Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective therapeutic targets for advanced patients are still lacking.Exosomes,tiny vesicles in body fluids,play a crucial role in tumor metastasis,immune regulation,and drug resistance.Interestingly,they can even serve as a biomarker for cancer diagnosis and prognosis.Studies have shown that exosomes can carry miRNA,mediate the polarization of M1/M2 macrophages,promote the proliferation and metastasis of cancer cells,and affect the prognosis of CRC.Since the gastrointestinal tract has many macrophages,understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial.This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.

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.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

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.

Colorectal cancer screening:The value of early detection and modern challenges

The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection rates.This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment.However,the adoption of CRC screening methods faces numerous challenges,including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity.Moreover,socioeconomic factors such as regional disparities,economic conditions,and varying levels of awareness affect screening uptake.The coronavirus disease 2019 pandemic further intensified these challenges,leading to reduced screening participation and increased waiting periods.Additionally,the growing prevalence of early-onset CRC necessitates innovative screening approaches.In response,research into new methodologies,including artificial intelligence-based systems,aims to improve the precision and accessibility of screening.Proactive measures by governments and health organizations to enhance CRC screening efforts are underway,including increased advocacy,improved service delivery,and international cooperation.The role of technological innovation and global health collaboration in advancing CRC screening is undeniable.Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening,making a significant impact on the fight against this disease.Given the rise in early-onset CRC,it is crucial for screening strategies to continually evolve,ensuring their effectiveness and applicability.

Establishing and clinically validating a machine learning model for predicting unplanned reoperation risk in colorectal cancer

BACKGROUND Colorectal cancer significantly impacts global health,with unplanned reoperations post-surgery being key determinants of patient outcomes.Existing predictive models for these reoperations lack precision in integrating complex clinical data.AIM To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients.METHODS Data of patients treated for colorectal cancer(n=2044)at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected.Patients were divided into an experimental group(n=60)and a control group(n=1984)according to unplanned reoperation occurrence.Patients were also divided into a training group and a validation group(7:3 ratio).We used three different machine learning methods to screen characteristic variables.A nomogram was created based on multifactor logistic regression,and the model performance was assessed using receiver operating characteristic curve,calibration curve,Hosmer-Lemeshow test,and decision curve analysis.The risk scores of the two groups were calculated and compared to validate the model.RESULTS More patients in the experimental group were≥60 years old,male,and had a history of hypertension,laparotomy,and hypoproteinemia,compared to the control group.Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation(P<0.05):Prognostic Nutritional Index value,history of laparotomy,hypertension,or stroke,hypoproteinemia,age,tumor-node-metastasis staging,surgical time,gender,and American Society of Anesthesiologists classification.Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility.CONCLUSION This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer,which can improve treatment decisions and prognosis.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver resection.Up to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after resection.AIM To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery.METHODS In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after chemotherapy.Various parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were measured.The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node status.The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient.RESULTS Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of 0.873.Furthermore,parameters from SEM showed substantial repeatability.CONCLUSION The developed nomogram,incorporating the pre-treatment DDC and the short axis of the largest lymph node,can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery.This nomogram was proven to be more valuable,exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI.The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.