Management of obstructed colorectal carcinoma in an emergency setting:An update

Colorectal carcinoma is common,particularly on the left side.In 20%of patients,obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced(stage II,III or even IV).Diagnosis is based on clinical presentation,plain abdominal radiogram,computed tomography(CT),CT colonography and positron emission tomography/CT.The best management strategy in terms of short-term operative or interventional and long-term oncological outcomes re-mains unknown.For the most common left-sided obstruction,the first choice should be either emergency surgery or endoscopic decompression by self-expen-dable metal stents or tubes.The operative plan should be either one-stage or two-stage resection.One-stage resection with on-table bowel decompression and irrigation can be accompanied or not accompanied by proximal defunctioning stoma(colostomy or ileostomy).Primary anastomosis is more convenient but has increased risks of anastomotic leakage and morbidity.Two-stage resection(Hart-mann’s procedure)is safer and the most widely used despite temporally affecting quality of life.Damage control surgery in high-risk frail patients is less frequently performed since it can be successfully substituted with endoscopic stenting or tubing.For the less common right-sided obstruction,one-stage surgical resection is more beneficial than endoscopic decompression.The role of minimally invasive surgery(laparoscopic or robotic)is a subject of debate.Emergency laparoscopic-assisted management is advantageous to some extent but requires much expertise due to inherent difficulties in dissecting the distended colon and the risk of rup-ture and subsequent septic complications.The decompressing stent as a bridge to elective surgery more substantially decreases the risks of morbidity and mortality than emergency surgery for decompression and has equivalent medium-term overall survival and disease-free survival rates.Its combination with neoadjuvant chemotherapy or radiation may have a positive effect on long-term oncological outcomes.Management plans are crucial and must be individualized to better fit each case.Core Tip:Acute obstruction is common in patients with more advanced colorectal carcinoma and may be the first manifestation mainly of left-sided obstruction and in elderly individuals.Emergency decompression is mandatory.Emergency surgical resection and primary anastomosis accompanied or not accompanied by proximal defunctioning stoma must be the first treatment choice for fit patients under 70 years.Hartmann’s two-stage procedure,although more preferable,must be the second alternative choice.Emergency endoscopic self-expendable metal stents must be preferred in unfit patients as a bridge to surgery and for palliative treatment in all inoperable cases.However,these basic management principles constitute a general direction.Decision-making is important and should be individualized.

Comprehensive next-generation sequencing reveals double primary colorectal carcinoma missed by diagnostic imaging: A case report

BACKGROUND Multiple primary colorectal carcinoma(MPCC)is a rare clinical disease,which is challenging to differentiate from metastatic disease using histopathological methods.Next-generation sequencing(NGS)has been employed to identify multiple primary cancers.CASE SUMMARY This study a rare case of a 63-year-old male patient diagnosed with MPCC by targeted NGS,which was initially missed by radiological evaluation.The patient was found to have two tumors located on the surface of the colorectum which had distinct genomic alterations.Based on wild-type KRAS detected in the unresected tumor,the patient benefited from the epidermal growth factor receptor(EGFR)inhibitor cetuximab treatment,but developed novel mutations including KIF5B-RET fusion,which provides a possible resistance mechanism to anti-EGFR therapy.CONCLUSION Our case highlights the necessity of using genetic testing for primary tumor diagnosis and the application of serial plasma circulating tumor DNA profiling for dynamic disease monitoring.

Hsa_circ_0136666 mediates the antitumor effect of curcumin in colorectal carcinoma by regulating CXCL1 via miR-1301-3p

BACKGROUND This study investigate the anti-tumor effect of curcumin and whether its mediated by hsa_circ_0136666 through miR-1301-3p/CXCL1 in colorectal carcinoma(CRC).Through multiple experiments,we have drawn the conclusion that curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis,hinting at a novel treatment option for curcumin to prevent CRC development.AIM To determine whether hsa_circ_0136666 involvement in curcumin-triggered CRC progression was mediated by sponging miR-1301-3p.METHODS Cell counting kit-8,colony-forming cell,5-ethynyl-2’-deoxyuridine,and flow cytometry assays were carried out to determine cell proliferation,apoptosis,and cell cycle progression.Real-time quantitative polymerase chain reaction quantified hsa_circ_0136666,miR-1301-3p,and chemokine(C-X-C motif)ligand 1(CXCL1),and western blot analysis determined CXCL1,B-cell lymphoma-2(Bcl-2),and Bcl-2 related X protein(Bax)protein levels.CircBank or starbase software was first used for the prediction of miR-1301-3p binding with hsa_circ_0136666 and CXCL1,followed by RNA pull-down,RNA immunoprecipitation,and dualluciferase reporter assay validation.In vivo experiments were implemented in a murine xenograft model.RESULTS Curcumin blocked CRC cell proliferation but boosted apoptosis.Moreover,elevated hsa_circ_0136666 Levels were observed in CRC cells,which were reduced by curcumin.In vitro,hsa_circ_0136666 overexpression abolished the antitumor activity of CRC cells.Mechanical analysis revealed the ability of hsa_circ_0136666 to sponge miR-1301-3p to modulate CXCL1 levels.CONCLUSION Curcumin inhibited CRC development through the hsa_circ_0136666/miR-1301-3p/CXCL1 axis,hinting at a novel treatment option for curcumin to prevent CRC development.

DNA methylation assay for colorectal carcinoma

Colorectal carcinoma(CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions in DNA mismatch repair genes.Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis.Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction(q PCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool q PCR methylation test may also be an enhanced tool for CRC and adenoma screening.

Significance of carbohydrate antigen 50 expression in colorectal carcinoma

Objective To evaluate the significance of carbohydrate antigen 50(CA50)expression in colorectal carcinoma.Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa.Results The expression of CA50 increased in normal colorectal mucosa,cancer distant mucosa,cancer adjacent mucosa and cancer mucosa,and there were significant differences among them(P<0.05).The expression of CA50 in colorectal carcinoma was correlated with the degree of differentiation,Duke's stage and lymphatic metastases(P<0.05).Conclusion The expression of CA50 can be used as a valuable index in evaluating the biological characteristics and prognosis of colorectal carcinoma.

Prognostic value of YKL-40 in colorectal carcinoma patients:A metaanalysis

BACKGROUND In recent years,the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated.However,whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified.AIM To identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients.METHODS Several electronic databases including the PubMed,EMBASE,Web of Science,CNKI,VIP and WanFang were searched for relevant studies.The hazard ratios(HR)and 95%confidence intervals(CI)were combined and the primary and secondary outcomes were overall survival(OS)and progression-free survival(PFS),respectively.All statistical analysis were conducted by STATA 15.0 software.RESULTS A total of nine studies involving 2545 patients were included.The pooled results indicated that YKL-40 was significantly associated with poor OS(HR=1.80,95%CI:1.32-2.45,P<0.001)and PFS(HR=1.62,95%CI:1.22-2.16,P=0.001).Subgroup analysis stratified by the treatment,tumor type and source of YKL-40 showed similar results.CONCLUSION Elevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients.YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.

THE EXPRESSION AND CLINICAL SIGNIFICANCE OF P21(WAF1/CIP1) AND CYCLIN D1 PROTEIN IN COLORECTAL CARCINOMA

Objective To study the effect of P21(WAF1/CIP1) and cyclin D1 and their relationship in colorectal carcinoma.Methods The expression of P21 and cyclin D1 was studied in 40 colorectal carcinoma and 10 normal tissues using S P immunohistochemical technique.Results Decreased expression of P12 and overexpression of cyclin D1 were revealed in colorectal carcinoma.Decreased expression of P21 was related to lymph node metastasis.No correlation was found between cyclin D1 and clinicopathological parameters.Conclusion Decreased expression of P21 and overexpression of cyclin D1 may be involved in colorectal tumorigenesis,and were associated with poor prognosis.No correlation was found between P21 and cyclin D1 in colorectal carcinoma.

Role of p38 Signaling Pathway in Pentagastrin-Regulated Cell Proliferation of Colorectal Carcinoma Cell Line HT-29

Objective: To investigate the effects and mechanisms of p38 signaling pathway in pentagastrin-regulated cell proliferation of colorectal carcinoma cell line HT-29. Methods: HT-29 cell line of colorectal carcinoma was in vitro incubated and divided into the control group, pentagastrin group, proglumide group, and pentagastrin + proglumide group. MTT reduction assay was performed to detect the proliferation status of HT-29 cell line and determine the optimal dosage of pentagastrin and proglumide. Annexin V-fluorescein isothiocyanate flow cytometry was used to detect the proliferation index (PI) and apoptosis rate (AR) of HT-29 cells. Reverse transcriptase polymerase chain reaction was performed to detect the mRNA expression of the pentagastrin receptor/cholecystokinin-B receptor (CCK-BR) and p38. The protein and phosphorylation levels of p38 were estimated by western blotting. Results: RT-PCR detection showed that CCK-BR mRNA was expressed in the HT-29 cell line. Pentagatrin improved HT-29 cell proliferation in dosage of 6.25 - 100 mg/L, and the optimal dosage of pentagastrin was 25.0 mg/L. Proglumide had no significant effect on the proliferation of HT-29 cells, but significantly inhibited the proliferation of HT-29 cells stimulated by pentagastrin when the dosage of proglumide was 8.0 - 128.0 mg/L, and the optimal dosage was 32.0 mg/L. The AR in the pentagastrin group was significantly lower than that in the control group and in the pentagastrin + proglumide group. The PI in the pentagastrin group was significantly higher than that in the control group and in the pentagastrin + proglumide group. P38 phosphorylation level in the pentagastrin group was significantly lower than that in the control group, and in the pentagastrin + proglumide group. There were no significant differences in the mRNA and protein expression of p38 in the control, pentagastrin, proglumide and pentagastrin + proglumide groups. Conclusion: Pentagastrin can improve proliferation of the CRC cell line HT-29 and inhibit apoptosis via the p38 signal transduction pathway. This mechanism may be associated with suppressed p38 protein phosphorylation level due to inhibition of proglumide, a gastrin receptor antagonist.

Codon 201 Mutation of DCC Gene and Tumor Biologic Behavior in Human Colorectal Carcinoma

Objective To explore the relationship between a point mutation of codon 201 in deleted in colorectal carcinoma (DCC) gene and the biological behavior of colorectal carcinoma. Methods Tumor tissues and matched adjacent normal colon mucosa collected in 35 patients during surgical resection for colorectal carcinoma were analyzed. Forty normal colon mucosa tissues obtained by biopsy from patients who had neither colorectal tumor nor a family history of colorectal cancer during colonscopic examination were used as control. Codon 201 mutation was detected with allele specific PCR and a restriction enzyme digestion method. The tumors were reviewed as clinical data, tumor location, histology, metastasis, and pathological staging (Dukes classification). Results The frequency of mutation at codon 201 in tumor tissue and corresponding adjacent normal mucosa was 71.4% and 60%, respectively, and either of the rates was significantly higher than that of normal control(32.5%). The point mutation rate in tumor tissues did not differ from that in the corresponding normal adjacent tissues. Statistic analysis showed that the mutation rate had no relationship to the sex, age of the patients, the histological pattern, differentiation, and invasion depth of the tumors. However, 93.8% of the mutation rate in colorectal cancer with lymph node invasion and/or distant metastasis is significantly higher than 52.6% of mutant rate in colorectal cancer without lymph nodes invasion or metastasis (P<0 05). Conclusion The point mutation at codon 201 of DCC gene is an early genetic event in colorectal cancer, and play some role in invasion and metastasis of colorectal carcinoma. It may serve as a useful genetic marker for identifying higher risk patients with colorectal carcinoma.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

Integrated bioinformatics identifies the dysregulation induced by aberrant gene methylation in colorectal carcinoma

Colorectal carcinoma(CRC)is one of the most common cancers,and is associated with a poor dlinical outcome.The key genes and potential prognostic markers in colorectal carcinoma remain to be identfed and explored for clinical application.DNA expression/methyl-ation profles were downloaded from the Gene Expression Omnibus(GEO)database to identify differentially expressed/methylated genes(DEGs and DEMs).A total of 255 genes and 372 genes were identified as being up-regulated and down-regulated,respectively,in GSE113513,GSE81558,and GSE89076.There were a total of 3350 hypermethylated genes and 443 hypomethylated genes identifed in GSE 48684.Twenty genes were found to be hypermethylated as well as down-regulated,and a functional enrichment analysis revealed that these genes were mainly involved in cancer-related pathways.Among these 20 genes,GPM6A,HAND2 and C2orf40 were related to poor outcomes in cancer patients based on a survival analysis.Concurrent decreases of GPM6A,HAND2 and C2orf40 protein expression were observed in highly-dif ferentiated colorectal carcinoma tissues,and higher expression levels were found in undifferentiated or minimally-differentiated colorectal carcinoma tissues.In conclusion,20 genes were found to be downregulated and hypermethylated in CRC,among which GPM6A,HAND2 and C2orf40 were explored for their potential prognostic value.

Prognostic nomograms for predicting overall survival and causespecific survival of signet ring cell carcinoma in colorectal cancer patients

BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.

Effect of macrophage capping protein on biological features of colorectal carcinoma

Objective To explore the expression of macrophage capping protein(CapG)in colorectal carcinoma tissues,and to investigate its effects on proliferation and migration of colorectal carcinoma cells.Methods From September10th,2015 to March 2nd,2016,the clinical data and tissues specimen of 84 patients with colorectal

Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P < 0.005). ELISA confirmed that MPO levels were significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand hostpathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.

Large endoscopic mucosal resection for colorectal tumors exceeding 4 cm

AIM:To evaluate the feasibility and the outcome of endoscopic mucosal resection(EMR)for large colorectal tumors exceeding 4 cm(LCRT)undergoing piecemeal resection. METHODS:From January 2005 to April 2008,146 digestive tumors larger than 2 cm were removed with the EMR technique in our department.Of these,34 tumors were larger than 4 cm and piecemeal resection was carried out on 26 colorectal tumors.The mean age of the patients was 71 years.The mean follow-up duration was 12 mo. RESULTS:LCRTs were located in the rectum,left colon,transverse colon and right colon in 58%,15%, 4%and 23%of cases,respectively.All were sessile tumors larger than 4 cm with a mean size of 4.9 cm (4-10 cm).According to the Paris classification,34%of the tumors were typeⅠs,58%typeⅡa,4%typeⅡb and 4%typeⅡc.Pathological examination showed tubulous adenoma in 31%,tubulo-villous adenoma in 27%,villous adenoma in 42%,high-grade dysplasia in38%,in situ carcinoma in 19%of the cases and mucosal carcinoma(m2)in 8%of the cases.The two cases(7.7%)of procedural bleeding that occurred were managed endoscopically and one small perforation was treated with clips.During follow-up,recurrence of the tumor occurred in three patients(12%),three of whom received endoscopic treatment. CONCLUSION:EMR for tumors larger than 4 cm is a safe and effective procedure that could compete with endoscopic submucosal dissection,despite providing incomplete histological assessment.

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

In the last two decades,the vision of a unique carcinogenesis model for colorectal carcinoma(CRC)has completely changed.In addition to the adenoma to carcinoma transition,colorectal carcinogenesis can also occur via the serrated pathway.Small non-coding RNA,known as microRNAs(miRNAs),were also shown to be involved in progression towards malignancy.Furthermore,increased expression of certain miRNAs in premalignant sessile serrated lesions(SSLs)was found,emphasizing their role in the serrated pathway progression towards colon cancer.Since miRNAs function as post-transcriptional gene regulators,they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly.In this review,we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma.Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway,which remains unstudied.

Genetic variation of TGF-BR2 as a protective genotype for the development of colorectal cancer in men

BACKGROUND The role of transforming growth factor beta(TGF-β)signaling,including both the cytokine and their receptors,in the etiology of colorectal cancer(CRC)has been of particular interest lately.AIM To investigate the association between promoter polymorphism in TGF-β receptor 2 TGF-BR2G^([-875])A with a CRC risk in a cohort of Bulgarian patients using a casecontrol gene association study approach,as well as the protein levels of TGF-β1 in the peripheral blood.METHODS A cohort of 184 CRC patients and 307 sex and age-matched healthy subjects were recruited in the study.A genotyping of the TGF-BR2G^([-875])A(rs3087465)polymorphism was performed by primer-introduced restriction analysespolymerase chain reaction approaches.RESULTS The frequency of TGF-BR2G^([-875])A genotype was decreased in male patients with CRC than in healthy men(31.3%vs 44.8%;P=0.058).Among males,the TGF-BR2G[-509]G genotype was related to a significantly increased risk of CRC development(OR=1.820,95%CI:0.985-3.362,P=0.055)than the GA+AA genotype.Also,TGF-BR2^([-875])*A-allele itself was rarer in men with CRC than healthy men(19.1%vs 26.9%,P=0.086)and was associated with a protective effect(OR=0.644;95%CI:0.389-1.066;P=0.086).Regarding the genotypes,we found that TGF-β1 serum levels were higher in GG genotype in healthy persons above 50 years than the CRC patients[36.3 ng/mL interquartile range(IQR)19.9-56.5 vs 22.4 ng/mL IQR 14.8-29.7,P=0.014].We found significant differences between higher levels of TGF-β1 serum levels in healthy controls above 50 years(GG genotype)and CRC patients(GG genotype)at the early stage(36.3 ng/mL IQR 19.9-56.5 vs 22.8 ng/mL IQR 14.6-28.6,P=0.037)and advanced CRC(36.3 ng/mL IQR 19.9-56.5 vs 21.6 ng/mL IQR 15.9-33.9,P=0.039).CONCLUSION In summary,our results demonstrated that TGF-BR2 AG and AA genotypes were associated with a reduced risk of CRC,as well as circulating levels of TGF-βcould prevent CRC development in a gender-specific manner.Notably,male carriers of TGF-BR2-875A allele genotypes had a lower risk of CRC development and progression,suggesting that TGF-BR2-875A/G polymorphism significantly affects the protective biological factors that also impact the risk of colon and rectal carcinogenesis.

Self-expanding metal stent placement and pathological alterations among obstructive colorectal cancer cases

BACKGROUND Experimental studies suggest that self-expanding metal stents(SEMSs)enhance the aggressive behavior of obstructive colorectal cancer.The influence of SEMS placement on pathological alterations remains to be elucidated.AIM To determine whether SEMS placement is associated with molecular or pathological features of colorectal carcinoma tissues.METHODS Using a nonbiased molecular pathological epidemiology database of patients with obstructive colorectal cancers,we examined the association of SEMS placement with molecular or pathological features,including tumor size,histological type,American Joint Committee on Cancer(AJCC)-pTNM stage,and mutation statuses in colorectal cancer tissues compared with the use of transanal tubes.A multivariable logistic regression model was used to adjust for potential confounders.RESULTS SEMS placement was significantly associated with venous invasion(P<0.01),but not with the other features examined,including tumor size,disease stage,mutation status,and lymphatic invasion.In both the univariable and multivariable models with adjustment for potential factors including tumor location,histological type,and AJCC-pT stage,SEMS placement was significantly associated with severe venous invasion(P<0.01).For the outcome category of severe venous invasion,the multivariable odds ratio for SEMS placement relative to transanal tube placement was 19.4(95%confidence interval:5.24–96.2).No significant differences of disease-free survival and overall survival were observed between SEMS and transanal tube groups.CONCLUSION SEMS placement might be associated with severe venous invasion in colorectal cancer tissue,providing an impetus for further investigations on the pathological alterations by SEMSs in colorectal cancer development.

Growth hormone and gastrointestinal malignancy:An intriguing link

Growth hormone(GH)excess is associated with several systemic complications,one of which is the increased risk of neoplastic processes particularly of the gastrointestinal(GI)tract.Among the GI neoplasms,the most reported association is with benign and malignant neoplasms of the colon.In the majority of published literature,an increased incidence of GI neoplasms,both colonic adenomas as well as colorectal carcinoma is reported.However,the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls.Many studies have reported an association of colorectal neoplasms with GH levels.Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1(IGF-1)signaling.Both GH and IGF-1 have proliferative,anti-apoptotic,and angiogenic effects on the systemic tissues leading to cellular proliferation.Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel,altered bile acids,deranged local immune response,shared genetic susceptibility factors and hyperinsulinemia.In view of the increased risk association,most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy.Recommendations for further follow-up colonoscopy differ but broadly,the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess.Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy,most cohort studies do not show an increased risk.

Molecular confocal laser endomicroscopy:A novel technique for in vivo cellular characterization of gastrointestinal lesions

While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.