Current and future perspectives in the management and treatment of colorectal cancer

In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality worldwide.The article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal cancer.It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC.Innovations in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical management.Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision oncology.This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.

Return to work in young and middle-aged colorectal cancer survivors:Factors influencing self-efficacy,fear,resilience,and financial toxicity

BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social lives.However,these survivors encounter significant challenges during their RTW process.Hence,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC survivors.AIM To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW outcomes.METHODS A cross-sectional investigation was adopted in this study.From September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in Chongqing.The investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and FT.To analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were used.RESULTS A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 days.Cox regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further improvement.Elevated levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC survivors.Health professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.

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

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

Lipid levels and insulin resistance markers in patients with colorectal cancer:Propensity score matching analysis

BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with CRC.Furthermore,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals.RESULTS Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG index.Conversely,they displayed elevated AI levels compared to their healthy counterparts.Patients in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early stages.Patients with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG index.Receiver operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC.The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.

Characteristics of gut microbiota dysbiosis in patients with colorectal polyps

This editorial,inspired by a recent study published in the World Journal of Gastrointestinal Oncology,covers the research findings on microbiota changes in various diseases.In recurrent colorectal polyps,the abundances of Klebsiella,Parvimonas,and Clostridium increase,while those of Bifidobacterium and Lactoba-cillus decrease.This dysbiosis may promote the formation and recurrence of polyps.Similar microbial changes have also been observed in colorectal cancer,inflammatory bowel disease,autism spectrum disorder,and metabolic syndrome,indicating the role of increased pathogens and decreased probiotics in these conditions.Regulating the gut microbiota,particularly by increasing probiotic levels,may help prevent polyp recurrence and promote gut health.This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.

Controversies around the treatment of peritoneal metastases of colorectal cancer

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer

BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.

Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

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.

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.

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.

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.

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.

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.