Development and validation of an online calculator to predict the pathological nature of colorectal tumors

BACKGROUND No single endoscopic feature can reliably predict the pathological nature of colorectal tumors(CRTs).AIM To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy.METHODS This was a single-center study.During the identification stage,530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group.Logistic regression analysis was performed.A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally.During the validation stage,two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists[five highly experienced endoscopists and five less experienced endoscopists(LEEs)]for external validation before and after systematic training.RESULTS A total of 750 patients were included,with an average age of 63.6±10.4 years.Early colorectal cancer(ECRC)was detected in 351(46.8%)patients.Tumor size,left semicolon site,rectal site,acanthosis,depression and an uneven surface were independent risk factors for ECRC.The C-index of the ECRC calculator prediction model was 0.906(P=0.225,Hosmer-Lemeshow test).For the LEEs,significant improvement was made in the sensitivity,specificity and accuracy(57.6%vs 75.5%;72.3%vs 82.4%;64.2%vs 80.2%;P<0.05),respectively,after training with the ECRC online calculator prediction model.CONCLUSION A novel online calculator including tumor size,location,acanthosis,depression,and uneven surface can accurately predict the pathological nature of ECRC.

Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: A meta-analysis

AIM: To compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the treatment of colorectal tumors.

Efficient hemostatic method for endoscopic submucosal dissection of colorectal tumors

AIM:To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection(ESD).METHODS:We studied 250 cases,in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2010.We developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick vessels.ESD was performed on 126 cases after adoption of the new method(the adopted group)and the new method was performed on 102 of these cases.ESD was performed on 124 cases before the adoption of the new method (the unadopted group).The details of the new method are as follows:firstly,a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure,and the coagulated vessel was removed using the forceps in the"endocut" mode without perioperative hemorrhage.Secondly,the partial surrounding submucosa was dissected using the forceps in the endocut mode.In the current study,we evaluated the efficacy of this method.RESULTS:Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative hemorrhage.Moderate perioperative hemorrhage occurred in five cases(4.9%);however,it was stopped by immediately reuse of the hemostatic forceps.The partial surrounding submucosa was dissected using the forceps in all 102 cases.In the adopted group,the median operation time was 105 min.The proportion of endoscopic en bloc resection was 92.8%(P<0.01)compared to 80.6%in the unadopted group.The postoperative hemorrhage and perforation rates were 2.3%and 2.3%.The rate of perforation was significantly lower than that in the unadopted group (9.6%,P<0.01).We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases,which were accomplished without any severe hemorrhage.CONCLUSION:The new method effectively treated submucosal thick vessels and shows promise for the prevention of perforation and perioperative hemorrhage in colonic ESD.

Correlation analysis of interstitial maturity and prognosis of colorectal cancer:Meta-analysis

BACKGROUND To investigate the relationship between interstitial maturity and prognosis of colorectal cancer.AIM To examine the correlation between interstitial maturity and the prognosis of colorectal cancer.METHODS The paper database PubMed,EMBASE,Cochranelibrary,Springerlink,CNKI,and Wanfang database were searched until December 2023."tumor stroma maturity""desmoplastic stroma reaction""desmoplastic reaction""stroma reaction""degree of stroma reaction""stroma classification""stroma density""colorectal cancer""colon cancer""rectal cancer""prognosis"were searched for the search terms.Two system assessors independently screened the literature quality according to the inclusion exclusion criteria,Quality evaluation and data extraction were performed for the included literatures,and meta-analysis was performed for randomized control trials included at using Review Manager 5.2 software.RESULTS Finally,data of 9849 patients with colorectal cancer from 19 cosets in 15 literatures were included,including 4339 patients with mature type(control group),3048 patients with intermediate type(intermediate group)and 2456 patients with immature type(immature group).The results of meta-analysis showed:Relapse-free survival[hazard ratio(HR)=2.66,95%confidence interval(CI):2.30-3.08;P<0.00001],disease-free survival(HR=3.68,95%CI:2.33-5.81;P<0.00001)and overall survival(HR=1.70,95%CI:1.53-1.87;P<0.00001)were significantly lower than those in mature group(control group);relapse-free survival(HR=1.36,95%CI:1.17-1.59;P<0.0001)and disease-free survival rate(HR=1.85,95%CI:1.53-2.24;P<0.0001)was significantly lower than the mature group(control group).CONCLUSION There is the correlation between tumor interstitial maturity and survival prognosis of colorectal cancer,and different degrees of tumor interstitial maturity have a certain impact on the quality of life of colorectal cancer patients.

Evaluation and analysis of neurocognitive dysfunction in patients with colorectal cancer after radical resection: A retrospective study

BACKGROUND With the continuous progress of colorectal cancer treatment technology,the survival rate of patients has improved significantly,but the problem of postoperative neurocognitive dysfunction has gradually attracted attention.AIM To analyze the risk factors for delayed postoperative neurocognitive recovery(DNR)after laparoscopic colorectal cancer surgery and constructed a risk prediction model to provide an evidence-based reference for the prevention and treatment of DNR after laparoscopic colorectal cancer surgery.METHODS The clinical data of 227 patients with colorectal cancer who underwent laparoscopic surgery and regional cerebral saturation oxygenation(rScO2)monitoring at our hospital from March 2020 to July 2022 were retrospectively analyzed.Common factors and potential factors affecting postoperative DNR were used as analysis variables,and univariate analysis and multifactor analysis were carried out step by step to determine the predictors of the model and construct a risk prediction model.The predictive performance of the model was assessed by the receiver operating characteristic(ROC)curve,the calibration curve was used to assess the fit of the model to the data,and a nomogram was drawn.In addition,30 patients who met the inclusion and exclusion criteria from January 2023 to July 2023 were selected for external verification of the prediction model.RESULTS The incidence of postoperative DNR in the modeling group was 15.4%(35/227).Multivariate analysis revealed that age,years of education,diabetes status,and the lowest rScO2 value were the independent influencing factors of postoperative DNR(all P<0.05).Accordingly,a DNR risk prediction model was constructed after laparoscopic colorectal cancer surgery.The area under the ROC curve of the model was 0.757(95%CI:0.676-0.839,P<0.001),and the Hosmer-Lemeshow test of the calibration curve suggested that the model was well fitted(P=0.516).The C-index for external validation of the row was 0.617.CONCLUSION The DNR risk prediction model associated with rScO2 monitoring can be used for individualized assessment of patients undergoing laparoscopic colorectal cancer surgery and provides a clinical basis for the prevention of DNR after surgery.

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.

Analysis of cancer-specific survival in patients with metastatic colorectal cancer: A evidence-based medicine study

BACKGROUND Metastatic colorectal cancer(mCRC)is a common malignancy whose treatment has been a clinical challenge.Cancer-specific survival(CSS)plays a crucial role in assessing patient prognosis and treatment outcomes.However,there is still li-mited research on the factors affecting CSS in mCRC patients and their corre-lation.AIM To predict CSS,we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC.METHODS Data were extracted from the United States Surveillance,Epidemiology,and End Results database from 2018 to 2023.All eligible patients were randomly divided into a training cohort and a validation cohort.The Cox proportional hazards model was used to investigate the independent risk factors for CSS.A new nomogram model was developed to predict CSS and was evaluated through internal and external validation.RESULTS A multivariate Cox proportional risk model was used to identify independent risk factors for CSS.Then,new CSS columns were developed based on these factors.The consistency index(C-index)of the histogram was 0.718(95%CI:0.712-0.725),and that of the validation cohort was 0.722(95%CI:0.711-0.732),indicating good discrimination ability and better performance than tumor-node-metastasis staging(C-index:0.712-0.732).For the training set,0.533,95%CI:0.525-0.540;for the verification set,0.524,95%CI:0.513-0.535.The calibration map and clinical decision curve showed good agreement and good potential clinical validity.The risk grading system divided all patients into three groups,and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups.The median CSS times in the low-risk,medium-risk,and high-risk groups were 36 months(95%CI:34.987-37.013),18 months(95%CI:17.273-18.727),and 5 months(95%CI:4.503-5.497),respectively.CONCLUSION Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC.In addition,the risk-grading system helps to accurately assess patient prognosis and guide treatment.

Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection

BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological assessment.Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD.METHODS This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected.We first assessed the difference in size with an absolute per-centage of the scaling discrepancy.Subsequently,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and<33%)with that of the incorrect scaling group(<-33%or>33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),respectively.As secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling groups.Finally,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate analysis.RESULTS The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in size.The incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimated in large tumors,but overestimated in small ones.This discrepancy appears worth understanding for optimal procedural preparation.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors

BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unresectable.AIM To investigate the factors associated with high-grade dysplasia(HGD)/carcinoma and deep SMI in colorectal LSTs.METHODS The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed.The characteristics of LST subtypes were compared.Risk factors for HGD/carcinoma and deep SMI(invasion depth≥1000μm)were determined using multivariate logistic regression.RESULTS A total of 323 patients with 341 colorectal LSTs were enrolled.Among the four subtypes,non-granular pseudodepressed(NG-PD)LSTs(85.5%)had the highest rate of HGD/carcinoma,followed by the granular nodular mixed(G-NM)(77.0%),granular homogenous(29.5%),and non-granular flat elevated(24.2%)subtypes.Deep SMI occurred commonly in NG-PD LSTs(12.9%).In the adjusted multivariate analysis,NG-PD[odds ratio(OR=16.8,P<0.001)and G-NM(OR=7.8,P<0.001)subtypes],size≥2 cm(OR=2.2,P=0.005),and positive non-lifting sign(OR=3.3,P=0.024)were independently associated with HGD/carcinoma.The NG-PD subtype(OR=13.3,P<0.001)and rectosigmoid location(OR=8.7,P=0.007)were independent risk factors for deep SMI.CONCLUSION Because of their increased risk for malignancy,it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD.Given their substantial risk for deep SMI,surgery needs to be considered for NG-PD LSTs located in the rectosigmoid,especially those with positive nonlifting signs.

Colorectal stenting for palliation and as a bridge to surgery:A 5-year follow-up study

AIM: To evaluate the long-term effectiveness of colonic stents in colorectal tumors causing large bowel obstruction.METHODS: We retrospectively analyzed data from 49 patients with colorectal cancer who had undergone colorectal stent placement between January 2008 and January 2013. Patients' symptoms,characteristics and clinicopathological data were obtained by reviewing medical records. The obstruction was diagnosed clinically and radiologically. Histopathological diagnosis was achieved endoscopically. Technical success rate(TSR)was defined as the ratio of patients with correctly placed SEMS upon stent deployment across the entire stricture length to total number of patients. Clinical success rate(CSR) was defined as the ratio of patients with technical success and successful maintenance of stent function before elective surgery(regardless of number of SEMS deployed) to total number of patients. The surgical success rate(SSR) of colorectal stent as a bridge to surgery was defined as the ratio of patients with successful surgical procedures. Unsuccessful surgical outcomes were defined as being due to insufficient colonic decompression. The technical,clinical,surgical success rates and complications after stenting were assessed.RESULTS: The median age of patients was 64(36 to 89). 44.9% of patients were male and 55.1% were female. Eighteen patients had the obstruction located in the rectum,15 patients in the rectosigmoid region,10 patients in the sigmoid region,and 6 patients had a tumor causing obstruction in the proximal colon. Each patient was categorized pathologically as stage 2(32.7%,16 patients) or stage 3(42.9%,21 patients) and 12 patients(24.4%) had metastatic disease. None of the patients received chemotherapy before stenting. Stenting was undertaken in 37 patients as a bridge to surgery,and in 12 patients stents were used for palliation. Median time to surgery after stenting was 30 ± 91.9 d. All surgery was completed in one single operation and thus no colostomy with stoma was needed. The median overall survival rate of patients with stage 2-3 colorectal cancer was 53.1 mo and stage 4 was 37.1 mo(P = 0.04). Metastatic colorectal patients who were treated palliatively with stents had backbone chemotherapy with oxaliplatin and/or irinotecan-based regimens plus antiangiogenic therapies,especially bevacizumab. Resolution of the obstruction and clinical improvement was achieved in all patients. The technical,clinical and surgical success rates were 95.9%,100% and 94.6%,respectively.CONCLUSION: The efficacy and safety of colonic stents was demonstrated both as a bridge to surgery and for palliative decompression. In addition,results emphasize the importance of the skills of the endoscopist in colonic stenting.

Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor

AIM： To investigate the functions of promoter hypermethylation of secreted frizzled-related proteins （sFRPs） genes in colorectal tumorigenesis and progression. METHODS： The promoter hypermethylation and expression of sFRP genes in 72 sporadic colorectal carcinomas, 33 adenomas, 18 aberrant crypt foci （ACF） and colorectal cancer cell lines RKO, HCT116 and SW480 were detected by methylation-specific PCR and reverse transcription PCR, respectively. RESULTS： None of the normal colorectal mucosa tissues showed methylated bands of any of four sFRP genes, sFRP1, 2, 4 and 5 were frequently methylated in colorectal carcinoma, adenoma and ACF （sFRP1 〉 85%, sFRP2 〉75%, sFRP5 〉 50%）, and the differences between three colorectal tissues were not significant （P 〉 0.05）. IVlethylation in colorectal tumors was more frequent than in normal mucosa and adjacent normal mucosa. The mRNA of sFRP1-5 genes was expressed in all normal colorectal mucosa samples. Expression of sFRP1, 2, 4 and 5 and sFRP1, 2 and 5 was downregulated in carcinoma and adenoma, respectively. The downregulation of sFRP2, 4 and 5 was more frequent in carcinoma than in adenoma. Expression of sFRP3 which promoter has no CpG island was downregulated in only a few of colorectal tumor samples （7/105）. The downregulation ofsFRP1, 2, 4 and 5 expression was significantly associated with promoter hypermethylation in colorectal tumor. After cells were treated by DAC/TSA combination, the silenced sFRP mRNA expression could be effectively re-expressed in colorectal cancer cell lines. CONCLUSION： Hypermethylation of sFRP genes is a common early event in the evolution of colorectal tumor, occurring frequently in ACF, which is regarded as the earliest lesion of multistage colorectal carcinogenesis. It appears to functionally silence sFRP genes expression. Methylation of sFRP1, 2 and 5 genes might serve as indicators for colorectal tumor.

Influence of FasL gene expression on hepatic metastasis of colorectal carcinoma

BACKGROUND: FasL expression was reported to be asso- ciated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and he- patic metastasis of colorectal carcinoma. METHODS: FasL gene expressions were examined with re- verse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent can- cerous mucosae, and metastasized liver focus from colorec- tal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method. RESULTS: FasL gene expression was detected in the prima- ry focus of colorectal cancer ( n = 58), adjacent cancerous mucosae ( n = 58), and metastasized hepatic tumor tissues (n =28). The positive rate of FasL expression was 24% (14/ 58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the me- tastasized hepatic tumor tissues was higher than that in the primary focus (χ2 = 43.49, P<0. 01) and adjacent cance- rous mucosae (χ2=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic me- tastasis (χ2=3.96, P <0.05). In vitro study positive expres- sion of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t = 11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells. CONCLUSIONS: FasL positive cancer cells are powerfullyresistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, show- ing stronger drug-resistance, and it facilitates hepatic me- tastasis.

Comparison between surgical outcomes of colorectal cancer in younger and elderly patients

AIM:To compare the outcome of surgical treatment of colorectal adenocarcinoma in elderly and younger patients.METHODS:The outcomes of 122 patients with colorectal adenocarcinoma who underwent surgical treatment between January 2004 and June 2009 were analyzed.The clinicopathological and blood biochemistry data of the younger group(<75 years) and the elderly group (≥75 years) were compared.RESULTS:There were no significant differences between the two groups in operation time,intraoperative blood loss,hospital stay,time to resumption of oral intake,or morbidity.The elderly group had a significantly higher rate of hypertension and cardiovascular disease.The perioperative serum total protein and albumin levels were significantly lower in the elderly than in the younger group.The serum carcinoembryonic antigen level was lower in the elderly than in the younger group,and there was a significant decreasing trend after the operation in the elderly group.CONCLUSION:The short-term outcomes of surgical treatment in elderly patients with colorectal adenocarcinoma were acceptable.Surgical treatment in elderly patients was considered a selectively effective approach.

Endoscopic submucosal dissection for large laterally spreading tumors involving the ileocecal valve and terminal ileum

Endoscopic submucosal dissection is a challenging technique that enables en-bloc resection for large colorectal tumors, as laterally spreading tumors, particularly difficult, if the ileocecal valve and terminal ileum is involved. Herein, we report on one of 4 cases. The procedures, using a bipolar needle knife (B-Knife) to reduce the perforation risk and carbon dioxide instead of conventional air insufflation for patient comfort, achieved curative resections without any complications.

Primary tumor resection in colorectal cancer with unresectable synchronous metastases: A review

At the time of diagnosis, 25% of patients with colorectal cancer(CRC) present with synchronous metastases, which are unresectable in the majority of patients. Whether primary tumor resection(PTR) followed by chemotherapy or immediate chemotherapy without PTR is the best therapeutic option in patients with asymptomatic CRC and unresectable metastases is a major issue, although unanswered to date. The aim of this study was to review all published data on whether PTR should be performed in patients with CRC and unresectable synchronous metastases. All aspects of the management of CRC were taken into account, es-pecially prognostic factors in patients with CRC and un-resectable metastases. The impact of PTR on survival and quality of life were reviewed, in addition to the characteristics of patients that could benefit from PTR and the possible underlying mechanisms. The risks of both approaches are reported. As no randomized study has been performed to date, we finally discussed how a therapeutic strategy's trial should be designed to pro-vide answer to this issue.

CORRELATIONSHIP BETWEEN CELLULAR DNA AND AgNOR PROTEIN CONTENT IN THE DEVELOPING COURSE OF COLORECTAL ADENOCARCINOMA

Cellular NDA and AgNOR Protein contents were evaluated byautomatic image analysis in tissue sections stained hy combined Feulgen-AgNOR staining method in 9 normal colonic mucosae, 45 colorectal adenomas and 27 adenocarcinomas. The results indicated that during the course that the normal colonical mucosa developed to colorectal adenocarcinoma via adenoma the DNA and AgNOR protein contents increased gradually and there were very significant correlationships between the DNA and the AgNOR protein contents of adenoma group and adenocarcinoma group. However, there were considerahle overlaping in the DNA or AgNOR Protein content and considerahle overlaping cases between adenoma and normal colonic mucosa groups and between adenoma and adenocarcinoma groups. But the overlaping scope in NDA and AgNOR Protein content and the number of overlaping cases were reduced significantly by assessing the correlationship between the DNA and AgNOR protein content. Therefore, it is much more reliable to distinguish colorectal adenomas from adnocarcinomas by using the correlationship between the cellular DNA and the AgNOR Protein contents in the same specimens.

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

From advanced diagnosis to advanced resection in early neoplastic colorectal lesions:Never-ending and trending topics in the 2020s

Colonoscopy represents the most widespread and effective tool for the prevention and treatment of early stage preneoplastic and neoplastic lesions in the panorama of cancer screening.In the world there are different approaches to the topic of colorectal cancer prevention and screening:different starting ages(45-50 years);different initial screening tools such as fecal occult blood with immunohistochemical or immune-enzymatic tests;recto-sigmoidoscopy;and colonoscopy.The key aspects of this scenario are composed of a proper bowel preparation that ensures a valid diagnostic examination,experienced endoscopist in detection of preneoplastic and early neoplastic lesions and open-minded to upcoming artificial intelligence-aided examination,knowledge in the field of resection of these lesions(from cold-snaring,through endoscopic mucosal resection and endoscopic submucosal dissection,up to advanced tools),and management of complications.

Similar fecal immunochemical test results in screening and referral colorectal cancer

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma

Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.