Results of selective decontamination with oral neomycin and metronidazole for major colorectal surgery in Australia:A cohort study

Objective The role of selective decontamination with oral antibiotics(OABs)and mechanical bowel preparation(MBP)prior to elective colorectal surgery is still widely debated.The objective of this study was to compare the outcomes of selective decontamination with neomycin,metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation.Methods Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital,a major Australian tertiary referral hospital,between June 2017 and January 2023.Comparisons between short-term outcomes of OAB+MBP and MBP/no preparation were made using prospectively collected data on length of stay(LOS),readmission,mortality within 30 days,anastomotic leakage(AL),surgical site infection(SSI),urinary tract infection,deep venous thrombosis and/or pulmonary embolism,pneumonia,and ileus.Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery.The Mann-Whitney U test was used to analyse continuous data,and the chi-square test was used for categorical data.Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL.Results Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI(2.7%vs.7.6%,p=0.043)and overall complications(32.7%vs.44.6%,p=0.020),particularly Clavien-Dindo 1 complications(7.3%vs.16.5%,p=0.009).However,the differences in AL(2.7%vs.4.5%,p=0.369)and organ/space SSI(1.3%vs.3.7%,p=0.327)were not statistically significant.The median LOS(6 d vs.6 d,p=0.370)was not different between the groups.Conclusion Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications.There was a trend to toward a lower AL,but this difference was not statistically significant.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma

BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.

Characteristics of gut microbiota in anastomotic leakage patients in cold zones post-colorectal cancer surgery: A high-throughput sequencing and propensity-score matching study

Objective:The study aimed to explore the association between gut microbiota and anastomotic leakage(AL)after surgery in colorectal cancer(CRC)patients from a frigid zone,based on high-throughput sequencing.Methods:A total of 98 CRC patients admitted to the Second Affiliated Hospital of Harbin Medical University from July 2018 to February 2019,who met the inclusion criteria,were included.Among these,10 patients were diagnosed as AL.After propensity-score matching of baseline characteristics,10 patients from the anastomotic leakage group(AG)and 10 patients from the normal group(NG)were finally included in this study.Fecal samples were collected,and total DNA was extracted for high-throughput sequencing and bioinformatic analysis.Results:Alpha diversity analysis showed no significant difference between the two groups,while beta diversity analysis revealed significant differences in principal components.Differential microbiota were classified as Proteobacteria at the phylum level(P=0.021).At the genus level,the abundances of Streptococcus(P=0.045),Citrobacter(P=0.008)and Klebsiella(P=0.002)were significantly different between the two groups.LEfSe analysis indicated that these genera contributed most to the differences between the groups.Conclusion:The characteristics of the gut microbiota in the AG and NG were significantly different,and these differences might be associated with AL in CRC patients from frigid zones.

Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes

BACKGROUND A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion,emigration,and vascular rebuilding of cancer cells.Cancer can be treated by targeting the pathways that trigger cell death.AIM To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs(DRLs),prognosis clinical survival,and treat patients with colorectal cancer with medications.METHODS Initially,we queried the Cancer Genome Atlas database to collect transcriptome,clinical,and genetic mutation data for colorectal cancer(CRC).Training and testing sets for CRC patient transcriptome data were generated randomly.Key long non-coding RNAs(lncRNAs)related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure,as well as univariate and multivariate Cox regression models.A prognostic model was then created after risk scoring.Also,Immune infiltration analysis,immune checkpoint analysis,and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups.Finally,we validated the differential expression and biomarker potential of riskpredictive lncRNAs through induction using both NCM460 and HT-29 cell lines,as well as a disulfidptosis model.RESULTS In this work,eight significant lncRNAs linked to disulfidptosis were found.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high-and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway.Furthermore,significant immune cell variations between the high-risk and low-risk groups were seen,as well as a higher incidence of immunological escape risk in the high-risk group.Finally,Epirubicin,bortezomib,teniposide,and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs.CONCLUSION Our findings emphasizes the role of disulfidptosis in regulating tumor development,therapeutic response,and patient survival in CRC patients.For the clinical treatment of CRC,these important LncRNAs could serve as viable therapeutic targets.

Evolution of laparoscopy in colorectal surgery:An evidencebased review

Open surgery for colorectal disease has progressed significantly over the past century from humble beginnings to form the mainstay of treatment for colorectal cancer and a number of benign conditions.Following the introduction of laparoscopic abdominal surgery,the next stage in the evolution of the specialty began in the 1990s with the first laparoscopic colonic resection.Following some early concerns regarding its safety and oncological efficacy during the latter part of that decade,laparoscopic colorectal surgery rapidly came into mainstream use in the early part of the current century with evidence supporting its use being made available from large scale randomised controlled trials.This article provides an evidence-based summary of this evolutionary process as it relates to both benign and malignant colorectal disease,as well as discussion of the next phase of new technologies such as robotic surgery.

Evolution and future of laparoscopic colorectal surgery

The advances of laparoscopic surgery since the early 1990 s have caused one of the largest technical revolutions in medicine since the detection of antibiotics(1922,Flemming),the discovery of DNA structure(1953,Watson and Crick),and solid organ transplantation(1954,Murray).Perseverance through a rocky start and increased familiarity with the chop-stick surgery in conjunction with technical refinements has resulted in a rapid expansion of the indications for minimally invasive surgery.Procedure-related factors initially contributed to this success and included the improved postoperative recovery and cosmesis,fewer wound complications,lower risk for incisional hernias and for subsequent adhesionrelated small bowel obstructions; the major breakthrough however came with favorable long-term outcomes data on oncological parameters.The future will have to determine the specific role of various technical approaches,define prognostic factors of success and true progress,and consider directing further innovation while potentially limiting approaches that do not add to patient outcomes.

Preoperative carcinoembryonic antibody is predictive of distant metastasis in pathologically T1 colorectal cancer after radical surgery

AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumor location,tumor size,lymph node status,and histological grade were recorded.Patients with and without metastasis were compared with regard to age,gender,CEA level and pathologic tumor characteristics using the independent t test orχ 2 test,as appropriate.Risk factors were determined by logistic regression analysis. RESULTS:Metastasis occurred in 6(3.8%)of the 159 patients during a median follow-up of 67.0(46.5%) mo.The rates of distant metastasis in patients with pT1 cancer of the colon and rectum were 6.7%and 2.9%, respectively(P<0.001).The rates of distant metastasis between male and female patients with T1 CRC were 6.25%and 1.27%,respectively(P<0.001).The most frequent site of distant metastasis was the liver. Age(P=0.522),gender(P=0.980),tumor location(P =0.330),tumor size(P=0.786),histological grade(P =0.509),and high serum CEA level(P=0.262)were not prognostic factors for lymph node metastasis.Univariate analysis revealed that age(P=0.231),gender(P =0.137),tumor location(P=0.386),and tumor size (P=0.514)were not risk factors for distant metastasis after radical resection for T1 colorectal cancer.Postoperative metastasis was only significantly correlated with high preoperative serum CEA level(P=0.001).Using multivariate logistic regression analysis,high preoperative serum CEA level(P=0.004;odds ratio 15.341; 95%CI 2.371-99.275)was an independent predictor for postoperative distant metastasis. CONCLUSION:The preoperative increased serum CEA level is a predictive risk factor for distant metastasis in CRC patients after radical resection.Adjuvant chemotherapy may be necessary in such patients,even if they have pT1 colorectal cancer.

Core value of laparoscopic colorectal surgery

Since laparoscopy was first used in cholecystectomy in 1987, it has developed quickly and has been used in most fields of traditional surgery. People have now accepted its advantages like small incision, quick recovery, light pain, beauty and short hospital stays. In early times, there are still controversies about the application of laparoscopy in malignant tumor treatments, especially about the problems of oncology efficacy, incision implantation and operation security. However, these concerns have been fully eliminated by evidences on the basis of evidence-basis medicine. In recent years, new minimally invasive technologies are appearing continually, but they still have challenges and may increase the difficulties of radical dissection and the risks of potential complications, so they are confined to benign or early malignant tumors. The core value of the laparoscopic technique is to ensure the high quality of tumor's radical resection and less complications. On the basis of this, it is allowed to pursue more minimally invasive techniques. Since the development of laparoscopic colorectal surgery is rapid and unceasing, we have reasons to believe that laparoscopic surgery will become gold standard for colorectal surgery in the near future.

New trends in colorectal surgery: Single port and natural orifice techniques

Single-incision laparoscopic surgery (SILS) and natural orifice transluminal endoscopic surgery (NOTES) have rapidly gained pace worldwide, potentially replacing conventional laparoscopic surgery (CLS) as the preferred colorectal surgery technique. Currently available data mainly consist of retrospective series analyzed in four meta-analyses. Despite conflicting results and lack of an objective comparison, SILS appears to offer cosmetic advantages over CLS. However, due to conflicting results and marked heterogeneity, present data fail to show significant differences in terms of operative time, postoperative morbidity profiles, port-site complications rates, oncological appropriateness, duration of hospitalization or cost when comparing SILS with conventional laparoscopy for colorectal procedures. The application of &#x0201c;pure&#x0201d; NOTES in humans remains limited to case reports because of unresolved issues concerning the ideal access site, distant organ reach, spatial orientation and viscera closure. Alternatively, minilaparoscopy-assisted natural orifice surgery techniques are being developed. The transanal &#x0201c;down-to-up&#x0201d; total mesorectum excision has been derived for transanal endoscopic microsurgery (TEM) and represents the most encouraging NOTES-derived technique. Preliminary experiences demonstrate good oncological and functional short-term outcomes. Large-scale randomized controlled trials are now mandatory to confirm the long-term SILS results and validate transanal TEM for the application of NOTES in humans.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

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.

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been increasing.With the popularization of endoscopic technology,a number of early CRC has been diagnosed.However,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and metastasis.AIM To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations.METHODS A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study.Results of blood routine test,liver and kidney function tests and tumor markers were collected before surgery.Patients were followed up through disease-specific database and telephone interviews.Tumor recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis.RESULTS We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of CRC.Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for OS.The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL.Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for OS.Given that these measures are easier to detect and more acceptable to patients,they may have broader applications.

How to decide on stent insertion or surgery in colorectal obstruction?

Colorectal cancer is one of the most common cancers in western society and malignant obstruction of the colon accounts for 8%-29% of all large bowel obstructions. Conventional treatment of these patients with malignant obstruction requiring urgent surgery is associated with a greater physiological insult on already nutritionally replete patients. Of late the utility of colonic stents has offered an option in the management of these patients in both the palliative and bridge to surgery setting. This has been the subject of many reviews which highlight its efficacy, particulary in reducing ostomy rates, allowing quicker return to oral diet, minimising extended post-operative recovery as well as some quality of life benefits. The uncertainity in managing patients with malignant colonic obstructions has lead to a more cautious use of stenting technology as community equipoise exists. Decision making analysis has demonstrated that surgeons' favored the use of stents in the palliative setting preferentially when compared to the curative setting where surgery was preferred. We aim to review the literature regarding the use of stent or surgery in colorectal obstruction, and then provide a discourse with regards to the approach in synthesising the data and applying it when deciding the appropriate application of stent or surgery in colorectal obstruction.

Predictors of dehydration and acute renal failure in patients with diverting loop ileostomy creation after colorectal surgery

BACKGROUND Despite the potential benefits of fecal diversion after low pelvic anastomosis in colorectal surgery, diverting loop ileostomy construction is related to significant rates of complications. AIM To determine potential predictors of high output related complications in patients with diverting loop ileostomy creation after colorectal surgery. METHODS Patients who underwent open and laparoscopic colorectal surgery requiring a diverting loop ileostomy from January 2010 to March 2018 were retrospectively analyzed. We included patients older than 18 years, who underwent colorectal surgery with primary low pelvic anastomosis, and with the creation of a diverting loop ileostomy, at elective or emergency settings for the treatment of benign or malignant conditions. Univariate and multivariate logistic regression analysis was used to determine the effect of the potential predictors on the rate of high output related complications. The high output related complications were dehydration and acute renal failure that required visits to the emergency department and hospitalizations. RESULTS Of the 102 patients included in the study, 23.5%(n = 24) suffered high output related complications. In this group of patients at least one visit to the emergency department (mean 1.6), and at least one readmission to the hospital was needed. The factors associated with high-output ileostomy, in the univariate analysis, were: urgent surgical intervention (OR = 2.6;P = 0.047), the development of postoperative complications (OR = 3;P = 0.024), have ulcerative colitis (OR = 4.8;P = 0.017), use of steroids (OR = 4.3;P = 0.010), mean output at discharge greater than 1000 mL/24 h (OR = 3.2;P = 0.016), and use of loperamide at discharge (OR = 2.8;P = 0.032). Multivariate logistic regression analysis identified two independent risk factors for high output related complications: ulcerative colitis [OR = 7.6 (95%CI: 1.81-31.95);P = 0.006], and ileostomy output at discharge ≥ 1000 mL/24 h [OR = 3.3 (1.18-9.37);P = 0.023]. CONCLUSION In our study, patients with ulcerative colitis and those with an ileostomy output above 1000 mL/24 h at discharge, were at increased risk of high output related complications.

Efficacy comparison of fruquintinib,regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Effectiveness of colonoscopy,immune fecal occult blood testing,and risk-graded screening strategies in colorectal cancer screening

BACKGROUND Colorectal cancer(CRC)is one of the most common malignant tumors,and early screening is crucial to improving the survival rate of patients.The combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC screening.Colonoscopy and fecal occult blood tests,when combined,can improve screening accuracy and early detection rates,thereby facilitating early intervention and treatment.However,certain risks and costs accompany it,making the establishment of a risk classification model crucial for accurate classification and management of screened subjects.AIM To evaluate the feasibility and effectiveness of colonoscopy,immune fecal occult blood test(FIT),and risk-graded screening strategies in CRC screening.METHODS Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023,participants who met the requirements were randomly assigned to a colonoscopy group,an FIT group,or a graded screening group at a ratio of 1:2:2(after risk assessment,the high-risk group received colonoscopy,the low-risk group received an FIT test,and the FITpositive group received colonoscopy).The three groups received CRC screening with different protocols,among which the colonoscopy group only received baseline screening,and the FIT group and the graded screening group received annual follow-up screening based on baseline screening.The primary outcome was the detection rate of advanced tumors,including CRC and advanced adenoma.The population participation rate,advanced tumor detection rate,and colonoscopy load of the three screening programs were compared.RESULTS A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled,including 8082 males(41.7%)and 11291 females(58.3%).The mean age was 60.05±6.5 years.Among them,3883 patients were enrolled in the colonoscopy group,7793 in the FIT group,and 7697 in the graded screening group.Two rounds of follow-up screening were completed in the FIT group and the graded screening group.The graded screening group(89.2%)and the colonoscopy group(42.3%)had the lowest overall screening participation rates,while the FIT group had the highest(99.3%).The results of the intentional analysis showed that the detection rate of advanced tumors in the colonoscopy group was greater than that of the FIT group[2.76%vs 2.17%,odds ratio(OR)=1.30,95%confidence interval(CI):1.01-1.65,P=0.037].There was no significant difference in the detection rate of advanced tumors between the colonoscopy group and the graded screening group(2.76%vs 2.35%,OR=1.9,95%CI:0.93-1.51,P=0.156),as well as between the graded screening group and the FIT group(2.35%vs 2.17%,OR=1.09%,95%CI:0.88-1.34,P=0.440).The number of colonoscopy examinations required for each patient with advanced tumors was used as an index to evaluate the colonoscopy load during population screening.The graded screening group had the highest colonoscopy load(15.4 times),followed by the colonoscopy group(10.2 times),and the FIT group had the lowest(7.8 times).CONCLUSION A hierarchical screening strategy based on CRC risk assessment is feasible for screening for CRC in the population.It can be used as an effective supplement to traditional colonoscopy and FIT screening programs.

Limonin inhibits the stemness of cancer stem-like cells derived from colorectal carcinoma cells potentially via blocking STAT3 signaling

BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal cancer(CRC)cells and cancer stem-like cells(CSCs),a subpopulation responsible for a poor prognosis,is unclear.AIM To evaluate the effects of limonin on CSCs derived from CRC cells.METHODS CSCs were collected by culturing CRC cells in serum-free medium.The cytotoxicity of limonin against CSCs and parental cells(PCs)was determined by cholecystokinin octapeptide-8 assay.The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.RESULTS As expected,limonin exerted inhibitory effects on CRC cell behaviors,including cell proliferation,migration,invasion,colony formation and tumor formation in soft agar.A relatively low concentration of limonin decreased the expression stemness hallmarks,including Nanog andβ-catenin,the proportion of aldehyde dehydrogenase 1-positive CSCs,and the sphere formation rate,indicating that limonin inhibits stemness without presenting cytotoxicity.Additionally,limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice.Moreover,limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression.Inhibition of Nanog andβ-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2μmol/L colievlin.CONCLUSION Taken together,these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

Natural orifice transluminal endoscopic surgery and localized resection for colorectal neoplasia

Modern methods of surgical intervention have the potential to provide effective,definitive management of early stage colorectal neoplasia by truly minimally invasive means.Margin-free clearance of early colonic neoplasia from within the intestinal lumen can already now be effected by endoscopic submucosal dissection in the colon and transluminal endoscopic microsurgery(TEM) in the rectum.Natural orifice transluminal endoscopic surgery(NOTES) offers the potential for providing transmural,full thickness excision as TEM does but at sites in the colon proximal to the rectum.The next conceptual advance required to make this practice an effective reality lies in evolving surgical regional staging strategies to effectively partner localized resective approaches and allow their deployment as definitive curative therapy.As the most compelling modality for nodal status ascertainment in the absence of lymphatic basin excision for other malignant disease processes,it seems timely to reconsider sentinel node biopsy in cancer of the colon and rectum.Whether by this means or indeed any other,such an ability to confidently identify patients with node negative disease would allow nascent innovative techniques flourish as definitive management for confined(N0) T1 and T2 cancers and so allow the application of available advanced technology for clinical benefit.Conversely,the development of a specific clinical niche for NOTES(whether,as here,for full thickness localized colonic excision or nodal staging alone) would greatly benefit the evolution and incorporation of this surgical strategy into clinical care paradigms.

Short-term outcomes after laparoscopic colorectal surgery in patients with previous abdominal surgery: A systematic review

AIM: To perform a systematic review focusing on shortterm outcomes after colorectal surgery in patients with previous abdominal open surgery(PAOS).METHODS: A broad literature search was performed with the terms "colorectal", "colectomy", "PAOS", "previous surgery" and "PAOS". Studies were included if their topic was laparoscopic colorectal surgery in patients with PAOS, whether descriptive or comparative. Endpoints of interest were conversion rates, inadvertent enterotomy and morbidity. Analysis of articles was made according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses.RESULTS: From a total of 394 citations, 13 full-texts achieved selection criteria to be included in the study. Twelve of them compared patients with and without PAOS. All studies were retrospective and comparative and two were case-matched. The selected studies comprised a total of 5005 patients, 1865 with PAOS. Among the later, only 294(16%) had history of a midline incision for previous gastrointestinal surgery. Conversion rates were significantly higher in 3 of 12 studies and inadvertent enterotomy during laparoscopywas more prevalent in 3 of 5 studies that disclosed this event. Morbidity was similar in the majority of studies. A quantitative analysis(meta-analysis) could not be performed due to heterogeneity of the studies. CONCLUSION: Conversion rates were slightly higher in PAOS groups, although not statistical significant in most studies. History of PAOS did not implicate in higher morbidity rates.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.