AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer(CRC)]. METHODS We performed a literature search using the ...AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer(CRC)]. METHODS We performed a literature search using the National Library of Medicine through Pub Med from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms(colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words(surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined nonadvanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC.RESULTS Our search strategy identified 592 candidate articlesof which 8 met inclusion criteria and were relevant for assessment of histology(low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma.CONCLUSION Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.展开更多
AIM: To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS: We conducted a retrospective cohort study using data from individuals who had ...AIM: To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS: We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. RESULTS: By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). CONCLUSION: Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults.展开更多
Objective The aim of the study was to investigate the discrepancy in nucleolin expression between colon adenoma and colon adenocarcinoma,explore the role of nucleolin expression in the carcinogenesis of colon adenocar...Objective The aim of the study was to investigate the discrepancy in nucleolin expression between colon adenoma and colon adenocarcinoma,explore the role of nucleolin expression in the carcinogenesis of colon adenocarcinoma,and determine the correlation of the nucleolin expression level with histological grade in colon adenocarcinoma.Methods In total,80 cases of colon adenocarcinoma with cancer-adjacent colon mucosa and 60 cases of colon adenomas were examined by immunohistochemistry using an antibody against nucleolin.Nucleolin expression levels in these groups were compared.The correlation between the nucleolin expression level and grade of colon adenocarcinoma was analyzed.Results Nucleolin expression is located in the nuclei of colon adenocarcinoma,colon adenoma,and cancer-adjacent colon mucosa tissues with different intensities.A semiquantitative evaluation using the Allred scoring system showed that the nucleolin immunostaining score in colon adenocarcinoma(7.8 ± 0.1) was significantly higher than those in colon adenoma(6.3 ± 0.2) and cancer-adjacent colon mucosa(5.4 ± 0.1;P < 0.01).The nucleolin immunostaining score in colon adenoma was significantly higher than that in cancer-adjacent colon mucosa(P < 0.01).Nucleolin expression levels in well-differentiated and moderately differentiated adenocarcinoma(6.8 ± 0.2) were significantly lower than those in poorly differentiated adenocarcinoma(8.0 ± 0.1;P < 0.01).Conclusion Increased nucleolin expression may play an important role in the process of malignant transformation of colon adenocarcinoma and predicts a poor prognosis.展开更多
AIM: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.METHODS: Wistar rats were divided into two groups that were fed either a high-fat diet(HF...AIM: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.METHODS: Wistar rats were divided into two groups that were fed either a high-fat diet(HFD) or a normalfat diet(ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor(TNF)-α, insulinlike growth factor(IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity(Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of pro-liferating cell nuclear antigen(PCNA), cyclooxygenase(COX)-2, cyclin D1, β-catenin and nuclear factor(NF)-κB proteins in the adenoma and comparative control tissues.RESULTS: The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, β-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining.CONCLUSION: HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.展开更多
AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltrans...AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.展开更多
AIM:To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments. METHODS:Data were collected from the computerized database of the...AIM:To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments. METHODS:Data were collected from the computerized database of the endoscopy unit of our tertiary referral center. We retrospectively analyzed 1101 consecutive colonoscopies that were performed over 1 year with standard white-light (n = 849) or HD+ with i-Scan (n = 252) instruments by four endoscopists, in an outpatient setting. Colonoscopy records included patients' main details and family history for colorectal cancer, indication for colonoscopy (screening, diagnostic or surveillance), type of instrument used (standard white-light or HD+ plus i-Scan), name of endoscopist and bowel preparation. Records for each procedure included whether the cecum was reached or not and the reason for failure, complications during or immediately after the procedure, and number, size, location and characteristics of the lesions. Polyps or protrudinglesions were defined as sessile or pedunculated, and nonprotruding lesions were defined according to Paris classification. For each lesion, histological diagnosis was recorded. RESULTS:Eight hundred and forty-nine colonoscopies were carried with the standard white-light video colonoscope and 252 with the HD+ plus i-Scan video colonoscope. The four endoscopists did 264, 300, 276 and 261 procedures, respectively; 21.6%, 24.0%, 21.7% and 24.1% of them with the HD+ plus i-Scan technique. There were no significant differences between the four endoscopists in either the number of procedures done or the proportions of each imaging technique used. Both techniques detected one or more mucosal lesions in 522/1101 procedures (47.4%). The overall number of lesions recognized was 1266; 645 in the right colon and 621 in the left. A significantly higher number of colonoscopies recognized lesions in the HD+ plus i-Scan mode (171/252 = 67.9%) than with the standard white-light technique (408/849 = 48.1%) (P < 0.0001). HD+ with i-Scan colonoscopies identified more lesions than standard white-light imaging (459/252 and 807/849, P < 0.0001), in the right or left colon (mean ± SD, 1.62 ± 1.36 vs 1.33 ± 0.73, P < 0.003 and 1.55 ± 0.98 vs 1.17 ± 0.93, P = 0.033), more lesions < 10 mm (P < 0.0001) or nonprotruding (P < 0.022), and flat polyps (P = 0.04). The cumulative mean number of lesions per procedure detected by the four endoscopists was significantly higher with HD+ with i-Scan than with standard white-light imaging (1.82 ± 2.89vs 0.95 ± 1.35,P < 0.0001). CONCLUSION:HD imaging with i-Scan during the withdrawal phase of colonoscopy significantly increased the detection of colonic mucosal lesions, particularly small and nonprotruding polyps.展开更多
Objective:To observe the significance of EZH2 and BMI-1 protein expression in the carcinogenesis process of colon serrated adenoma(SSA/P).Methods:Hematoxylin-eosin(HE)staining was used to observe the morphological cha...Objective:To observe the significance of EZH2 and BMI-1 protein expression in the carcinogenesis process of colon serrated adenoma(SSA/P).Methods:Hematoxylin-eosin(HE)staining was used to observe the morphological characteristics of normal tissues,hyperplastic polyp(HP),SSA/P and colon cancer.Immunohistochemical staining was used to detect the expression of EZH2 and BMI-1 protein.The relative expression of EZH2 and BMI-1 was detected by qRT-PCR.Results:Compared with normal tissues,HP and colon cancer tissues,SSA/P showed serrated glandular hyperplasia,glandular dilatation,and deep nuclear staining,which had certain atypia.The positive expression rates of EZH2 and BMI-1 protein were 53.3%and 56%,which were close to those of colon cancer(66.7% and 76.6%)and higher than those of normal group and HP(16% and 8%,P<0.05).The relative expression of EZH2 and BMI-1 in SSA/P tissue was significantly higher than that in normal group and HP,but lower than that in carcinogenesis group(P<0.05).Conclusion:EZH2 and BMI-1 play an important role in the carcinogenesis of colon serrated adenoma,and can be used as the primary screening index before carcinogenesis.展开更多
Objective: To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods: Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Pr...Objective: To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods: Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) after mRNA extraction. Results: The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue (P〈0.01). GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer (P〈0.01), but no relationship with gender and age (P〉0.05). GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age (P〉0.05). The mRNA expression of GRP78 and GRP94 was consistent with the proteins (P〈0.01), but there is no correlation between overexpression of GRP78 and GRP94 (P〉0.05), and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages (P〉0.05). Conclusion: Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.展开更多
AIM: To evaluate the efficacy of cap-assisted colonoscopy(CAC) for detection of colorectal polyps and adenomas according to the lesion location and endoscopist training level.METHODS: Patients 20 years or older, who u...AIM: To evaluate the efficacy of cap-assisted colonoscopy(CAC) for detection of colorectal polyps and adenomas according to the lesion location and endoscopist training level.METHODS: Patients 20 years or older, who underwent their first screening colonoscopy in a single tertiary center from May 2011 to December 2012 were enrolled in this study. All patients underwent either CAC or standard colonoscopy(SC), and all of the procedures were performed by 11 endoscopists(8 trainees and 3 experts). All procedures were performed with highdefinition colonoscopes and narrow band imaging. The eight trainees had experiences of performing 150 to 500 colonoscopies, and the three experts had experiences of performing more than 3000 colonoscopies. A 4-mmlong transparent cap was attached to the end of a colonoscope in the CAC group. We retrospectively evaluated the number of polyps and adenomas, polyp detection rate(PDR), and the number of adenomas and adenoma detection rate(ADR) according to the lesion location and endoscopist training level between CAC and SC. We also evaluated the number of polyps and adenomas according to their size between CAC and SC.RESULTS: Overall, PDR and ADR using CAC were significantly higher than those using SC for both whole colon(48.5% vs 40.7%, P = 0.012; 35.7% vs 28.3%, P = 0.012) and right-side colon(35.3% vs 26.6%, P = 0.002; 27.0% vs 16.9%, P < 0.001). The number of polyps and adenomas per patient using CAC was significantly higher than that using SC for both the whole colon(1.07 ± 1.59 vs 0.82 ± 1.31, P = 0.008; 0.72 ± 1.32 vs 0.50 ± 1.01, P = 0.003) and right-side colon(0.66 ± 1.18 vs 0.41 ± 0.83, P < 0.001; 0.46 ± 0.97 vs 0.25 ± 0.67, P < 0.001). In the trainee group, the PDR and ADR using CAC were significantly higher than those using SC for both the whole colon(46.7% vs 39.7%, P = 0.040; 33.9% vs 26.0%, P =0.012) and right-side colon(34.2% vs 26.5%, P = 0.015; 25.3% vs 15.9%, P = 0.001). In the expert group, the PDR and ADR using CAC were significantly higher than those using SC only for the right-side colon(42.1% vs 27.0%, P =0.035; 36.8% vs 21.0%, P = 0.020).CONCLUSION: CAC is more effective than SC for detection of colorectal polyps and adenomas, especially when performed by trainees and when the lesions are located in the right-side colon.展开更多
A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectom...A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.展开更多
AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy.METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (me...AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy.METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (mean age 60 years, 65% males,without prior history of colorectal examination). Neoplasms were classified as diminutive adenoma (5 mm or less),small adenoma (6-9 mm), advanced adenoma (10 mm or more, with villous component or high-grade dysplasia)and cancer (invasive adenocarcinoma). The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal colon (from cecum to descending colon).RESULTS: The trend of the prevalence of advanced proximal adenoma was to increase with severe rectosigmoid findings, while the prevalence of proximal colon cancer did not increase with severe rectosigmoid findings. Among the 157 patients with proximal colon cancer, 74% had no neoplasm in the rectosigmoid colon. Multivariate logisticregression analysis revealed that age was the main predictor of proximal colon cancer and existence of rectosigmoid adenoma was not a predictor of proximal colon cancer.CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening, especially in older populations.展开更多
AIM:To evaluate accuracy of in vivo diagnosis of adenomatous vs non-adenomatous polyps using i-SCAN digital chromoendoscopy compared with high-definition white light.METHODS:This is a single-center comparative effecti...AIM:To evaluate accuracy of in vivo diagnosis of adenomatous vs non-adenomatous polyps using i-SCAN digital chromoendoscopy compared with high-definition white light.METHODS:This is a single-center comparative effectiveness pilot study.Polyps(n = 103) from 75 averagerisk adult outpatients undergoing screening or surveillance colonoscopy between December 1,2010 and April 1,2011 were evaluated by two participating endoscopists in an academic outpatient endoscopy center.Polyps were evaluated both with high-definition white light and with i-SCAN to make an in vivo prediction of adenomatous vs non-adenomatous pathology.We determined diagnostic characteristics of i-SCAN and highdefinition white light,including sensitivity,specificity,and accuracy,with regards to identifying adenomatous vs non-adenomatous polyps.Histopathologic diagnosis was the gold standard comparison.RESULTS:One hundred and three small polyps,detected from forty-three patients,were included in the analysis.The average size of the polyps evaluated in the analysis was 3.7 mm(SD 1.3 mm,range 2 mm to 8 mm).Formal histopathology revealed that 54/103(52.4%) were adenomas,26/103(25.2%) were hyperplastic,and 23/103(22.3%) were other diagnoses include "lymphoid aggregates","non-specific colitis," and "no pathologic diagnosis." Overall,the combined accuracy of endoscopists for predicting adenomas was identical between i-SCAN(71.8%,95%CI:62.1%-80.3%) and high-definition white light(71.8%,95%CI:62.1%-80.3%).However,the accuracy of each endoscopist differed substantially,where endoscopist A demonstrated 63.0% overall accuracy(95%CI:50.9%-74.0%) as compared with endoscopist B demonstrating 93.3% overall accuracy(95%CI:77.9%-99.2%),irrespective of imaging modality.Neither endoscopist demonstrated a significant learning effect with i-SCAN during the study.Though endoscopist A increased accuracy using i-SCAN from 59%(95%CI:42.1%-74.4%) in the first half to 67.6%(95%CI:49.5%-82.6%) in the second half,and endoscopist B decreased accuracy using i-SCAN from 100%(95%CI:80.5%-100.0%) in the first half to 84.6%(95%CI:54.6%-98.1%) in the second half,neither of these differences were statistically significant.CONCLUSION:i-SCAN and high-definition white light had similar efficacy predicting polyp histology.Endoscopist training likely plays a critical role in diagnostic test characteristics and deserves further study.展开更多
In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classi...In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps(HPs), traditional serrated adenomas(TSAs), and sessile serrated adenoma/polyps(SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging(AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging(NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as Ⅱ-dilatation pit(Ⅱ-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.展开更多
AIM:To prospectively investigate the detection rate of laterally spreading tumors(LSTs)of the colorectum by computed tomography(CT)colonography(CTC).METHODS:Patients with LSTs measuring≥20 mm detected during colonosc...AIM:To prospectively investigate the detection rate of laterally spreading tumors(LSTs)of the colorectum by computed tomography(CT)colonography(CTC).METHODS:Patients with LSTs measuring≥20 mm detected during colonoscopy were prospectively enrolled in the study.All patients underwent colonoscopy and subsequent CTC on the same day.CTC was performed using multi-detector CT without contrast in the prone and supine positions.Two radiologists blinded to the existence of LSTs read the virtual endoscopic images as well as 2-D images.LSTs were classified into granular and non-granular types based on colonoscopic appearance.RESULTS:Forty-seven pathologically proven LSTs were evaluated prospectively.Histology included adenomas in 19,mucosal cancers in 19 and T1 cancers in 9.The mean diameter of the LSTs was 35.1 mm.Twenty-eight(60%)LSTs were correctly identified by CTC,and the configuration was similar to the colonoscopic appearance in most cases.Detection rate for the granular type was significantly higher than that for the nongranular type(71%vs 31%,P=0.013).Detection rate of adenomas was significantly lower than mucosal cancers(32%vs 79%,P=0.008)and T1 cancers(32%vs 78%,P=0.042).CONCLUSION:The detection rate of LSTs by CTC,particularly the non-granular type was not acceptable.Practitioners should be aware of the relatively low detection rate when using CTC.展开更多
AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). ME...AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.展开更多
基金Supported by(in part through)awarded grants from the National Institutes of Health,No.K08DK090150 to Calderwood AH,No.U01CA111257 to Roy HK,No.R01CA165309 to Roy HK,and No.R01CA156186 to Roy HKAmerican Cancer Society Research Scholar Grant,No.RSG-14-034-01-CPPB to Lasser KE
文摘AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer(CRC)]. METHODS We performed a literature search using the National Library of Medicine through Pub Med from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms(colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words(surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined nonadvanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC.RESULTS Our search strategy identified 592 candidate articlesof which 8 met inclusion criteria and were relevant for assessment of histology(low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma.CONCLUSION Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.
基金Supported by The Biomedical Research Center Promotion Fund of the Ulsan University Hospital (UUH-2008-08)
文摘AIM: To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS: We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. RESULTS: By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). CONCLUSION: Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults.
文摘Objective The aim of the study was to investigate the discrepancy in nucleolin expression between colon adenoma and colon adenocarcinoma,explore the role of nucleolin expression in the carcinogenesis of colon adenocarcinoma,and determine the correlation of the nucleolin expression level with histological grade in colon adenocarcinoma.Methods In total,80 cases of colon adenocarcinoma with cancer-adjacent colon mucosa and 60 cases of colon adenomas were examined by immunohistochemistry using an antibody against nucleolin.Nucleolin expression levels in these groups were compared.The correlation between the nucleolin expression level and grade of colon adenocarcinoma was analyzed.Results Nucleolin expression is located in the nuclei of colon adenocarcinoma,colon adenoma,and cancer-adjacent colon mucosa tissues with different intensities.A semiquantitative evaluation using the Allred scoring system showed that the nucleolin immunostaining score in colon adenocarcinoma(7.8 ± 0.1) was significantly higher than those in colon adenoma(6.3 ± 0.2) and cancer-adjacent colon mucosa(5.4 ± 0.1;P < 0.01).The nucleolin immunostaining score in colon adenoma was significantly higher than that in cancer-adjacent colon mucosa(P < 0.01).Nucleolin expression levels in well-differentiated and moderately differentiated adenocarcinoma(6.8 ± 0.2) were significantly lower than those in poorly differentiated adenocarcinoma(8.0 ± 0.1;P < 0.01).Conclusion Increased nucleolin expression may play an important role in the process of malignant transformation of colon adenocarcinoma and predicts a poor prognosis.
基金Supported by the National Natural Science Foundation of China,No.81230057
文摘AIM: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.METHODS: Wistar rats were divided into two groups that were fed either a high-fat diet(HFD) or a normalfat diet(ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor(TNF)-α, insulinlike growth factor(IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity(Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of pro-liferating cell nuclear antigen(PCNA), cyclooxygenase(COX)-2, cyclin D1, β-catenin and nuclear factor(NF)-κB proteins in the adenoma and comparative control tissues.RESULTS: The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, β-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining.CONCLUSION: HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.
基金Supported by The Technical University of Dresden/Germany
文摘AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.
文摘AIM:To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments. METHODS:Data were collected from the computerized database of the endoscopy unit of our tertiary referral center. We retrospectively analyzed 1101 consecutive colonoscopies that were performed over 1 year with standard white-light (n = 849) or HD+ with i-Scan (n = 252) instruments by four endoscopists, in an outpatient setting. Colonoscopy records included patients' main details and family history for colorectal cancer, indication for colonoscopy (screening, diagnostic or surveillance), type of instrument used (standard white-light or HD+ plus i-Scan), name of endoscopist and bowel preparation. Records for each procedure included whether the cecum was reached or not and the reason for failure, complications during or immediately after the procedure, and number, size, location and characteristics of the lesions. Polyps or protrudinglesions were defined as sessile or pedunculated, and nonprotruding lesions were defined according to Paris classification. For each lesion, histological diagnosis was recorded. RESULTS:Eight hundred and forty-nine colonoscopies were carried with the standard white-light video colonoscope and 252 with the HD+ plus i-Scan video colonoscope. The four endoscopists did 264, 300, 276 and 261 procedures, respectively; 21.6%, 24.0%, 21.7% and 24.1% of them with the HD+ plus i-Scan technique. There were no significant differences between the four endoscopists in either the number of procedures done or the proportions of each imaging technique used. Both techniques detected one or more mucosal lesions in 522/1101 procedures (47.4%). The overall number of lesions recognized was 1266; 645 in the right colon and 621 in the left. A significantly higher number of colonoscopies recognized lesions in the HD+ plus i-Scan mode (171/252 = 67.9%) than with the standard white-light technique (408/849 = 48.1%) (P < 0.0001). HD+ with i-Scan colonoscopies identified more lesions than standard white-light imaging (459/252 and 807/849, P < 0.0001), in the right or left colon (mean ± SD, 1.62 ± 1.36 vs 1.33 ± 0.73, P < 0.003 and 1.55 ± 0.98 vs 1.17 ± 0.93, P = 0.033), more lesions < 10 mm (P < 0.0001) or nonprotruding (P < 0.022), and flat polyps (P = 0.04). The cumulative mean number of lesions per procedure detected by the four endoscopists was significantly higher with HD+ with i-Scan than with standard white-light imaging (1.82 ± 2.89vs 0.95 ± 1.35,P < 0.0001). CONCLUSION:HD imaging with i-Scan during the withdrawal phase of colonoscopy significantly increased the detection of colonic mucosal lesions, particularly small and nonprotruding polyps.
文摘Objective:To observe the significance of EZH2 and BMI-1 protein expression in the carcinogenesis process of colon serrated adenoma(SSA/P).Methods:Hematoxylin-eosin(HE)staining was used to observe the morphological characteristics of normal tissues,hyperplastic polyp(HP),SSA/P and colon cancer.Immunohistochemical staining was used to detect the expression of EZH2 and BMI-1 protein.The relative expression of EZH2 and BMI-1 was detected by qRT-PCR.Results:Compared with normal tissues,HP and colon cancer tissues,SSA/P showed serrated glandular hyperplasia,glandular dilatation,and deep nuclear staining,which had certain atypia.The positive expression rates of EZH2 and BMI-1 protein were 53.3%and 56%,which were close to those of colon cancer(66.7% and 76.6%)and higher than those of normal group and HP(16% and 8%,P<0.05).The relative expression of EZH2 and BMI-1 in SSA/P tissue was significantly higher than that in normal group and HP,but lower than that in carcinogenesis group(P<0.05).Conclusion:EZH2 and BMI-1 play an important role in the carcinogenesis of colon serrated adenoma,and can be used as the primary screening index before carcinogenesis.
基金supported by a grant from the Doctoral science Foundation of Liaoning Province (No.20041052)
文摘Objective: To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods: Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) after mRNA extraction. Results: The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue (P〈0.01). GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer (P〈0.01), but no relationship with gender and age (P〉0.05). GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age (P〉0.05). The mRNA expression of GRP78 and GRP94 was consistent with the proteins (P〈0.01), but there is no correlation between overexpression of GRP78 and GRP94 (P〉0.05), and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages (P〉0.05). Conclusion: Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.
基金Supported by A 2-year research grant of Pusan National University
文摘AIM: To evaluate the efficacy of cap-assisted colonoscopy(CAC) for detection of colorectal polyps and adenomas according to the lesion location and endoscopist training level.METHODS: Patients 20 years or older, who underwent their first screening colonoscopy in a single tertiary center from May 2011 to December 2012 were enrolled in this study. All patients underwent either CAC or standard colonoscopy(SC), and all of the procedures were performed by 11 endoscopists(8 trainees and 3 experts). All procedures were performed with highdefinition colonoscopes and narrow band imaging. The eight trainees had experiences of performing 150 to 500 colonoscopies, and the three experts had experiences of performing more than 3000 colonoscopies. A 4-mmlong transparent cap was attached to the end of a colonoscope in the CAC group. We retrospectively evaluated the number of polyps and adenomas, polyp detection rate(PDR), and the number of adenomas and adenoma detection rate(ADR) according to the lesion location and endoscopist training level between CAC and SC. We also evaluated the number of polyps and adenomas according to their size between CAC and SC.RESULTS: Overall, PDR and ADR using CAC were significantly higher than those using SC for both whole colon(48.5% vs 40.7%, P = 0.012; 35.7% vs 28.3%, P = 0.012) and right-side colon(35.3% vs 26.6%, P = 0.002; 27.0% vs 16.9%, P < 0.001). The number of polyps and adenomas per patient using CAC was significantly higher than that using SC for both the whole colon(1.07 ± 1.59 vs 0.82 ± 1.31, P = 0.008; 0.72 ± 1.32 vs 0.50 ± 1.01, P = 0.003) and right-side colon(0.66 ± 1.18 vs 0.41 ± 0.83, P < 0.001; 0.46 ± 0.97 vs 0.25 ± 0.67, P < 0.001). In the trainee group, the PDR and ADR using CAC were significantly higher than those using SC for both the whole colon(46.7% vs 39.7%, P = 0.040; 33.9% vs 26.0%, P =0.012) and right-side colon(34.2% vs 26.5%, P = 0.015; 25.3% vs 15.9%, P = 0.001). In the expert group, the PDR and ADR using CAC were significantly higher than those using SC only for the right-side colon(42.1% vs 27.0%, P =0.035; 36.8% vs 21.0%, P = 0.020).CONCLUSION: CAC is more effective than SC for detection of colorectal polyps and adenomas, especially when performed by trainees and when the lesions are located in the right-side colon.
文摘A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.
文摘AIM: To review the risk of proximal colon cancer in patients undergoing colonoscopy.METHODS: We estimated the risk of advanced proximal adenomas and cancers in 6 196 consecutive patients that underwent colonoscopy (mean age 60 years, 65% males,without prior history of colorectal examination). Neoplasms were classified as diminutive adenoma (5 mm or less),small adenoma (6-9 mm), advanced adenoma (10 mm or more, with villous component or high-grade dysplasia)and cancer (invasive adenocarcinoma). The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal colon (from cecum to descending colon).RESULTS: The trend of the prevalence of advanced proximal adenoma was to increase with severe rectosigmoid findings, while the prevalence of proximal colon cancer did not increase with severe rectosigmoid findings. Among the 157 patients with proximal colon cancer, 74% had no neoplasm in the rectosigmoid colon. Multivariate logisticregression analysis revealed that age was the main predictor of proximal colon cancer and existence of rectosigmoid adenoma was not a predictor of proximal colon cancer.CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening, especially in older populations.
基金Supported by An Unrestricted Educational Grant from PENTAX Medical CompanyA Career Development Research Awardfrom the American Society for Gastrointestinal Endoscopy,to Dr.Gellad
文摘AIM:To evaluate accuracy of in vivo diagnosis of adenomatous vs non-adenomatous polyps using i-SCAN digital chromoendoscopy compared with high-definition white light.METHODS:This is a single-center comparative effectiveness pilot study.Polyps(n = 103) from 75 averagerisk adult outpatients undergoing screening or surveillance colonoscopy between December 1,2010 and April 1,2011 were evaluated by two participating endoscopists in an academic outpatient endoscopy center.Polyps were evaluated both with high-definition white light and with i-SCAN to make an in vivo prediction of adenomatous vs non-adenomatous pathology.We determined diagnostic characteristics of i-SCAN and highdefinition white light,including sensitivity,specificity,and accuracy,with regards to identifying adenomatous vs non-adenomatous polyps.Histopathologic diagnosis was the gold standard comparison.RESULTS:One hundred and three small polyps,detected from forty-three patients,were included in the analysis.The average size of the polyps evaluated in the analysis was 3.7 mm(SD 1.3 mm,range 2 mm to 8 mm).Formal histopathology revealed that 54/103(52.4%) were adenomas,26/103(25.2%) were hyperplastic,and 23/103(22.3%) were other diagnoses include "lymphoid aggregates","non-specific colitis," and "no pathologic diagnosis." Overall,the combined accuracy of endoscopists for predicting adenomas was identical between i-SCAN(71.8%,95%CI:62.1%-80.3%) and high-definition white light(71.8%,95%CI:62.1%-80.3%).However,the accuracy of each endoscopist differed substantially,where endoscopist A demonstrated 63.0% overall accuracy(95%CI:50.9%-74.0%) as compared with endoscopist B demonstrating 93.3% overall accuracy(95%CI:77.9%-99.2%),irrespective of imaging modality.Neither endoscopist demonstrated a significant learning effect with i-SCAN during the study.Though endoscopist A increased accuracy using i-SCAN from 59%(95%CI:42.1%-74.4%) in the first half to 67.6%(95%CI:49.5%-82.6%) in the second half,and endoscopist B decreased accuracy using i-SCAN from 100%(95%CI:80.5%-100.0%) in the first half to 84.6%(95%CI:54.6%-98.1%) in the second half,neither of these differences were statistically significant.CONCLUSION:i-SCAN and high-definition white light had similar efficacy predicting polyp histology.Endoscopist training likely plays a critical role in diagnostic test characteristics and deserves further study.
文摘In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps(HPs), traditional serrated adenomas(TSAs), and sessile serrated adenoma/polyps(SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging(AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging(NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as Ⅱ-dilatation pit(Ⅱ-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.
文摘AIM:To prospectively investigate the detection rate of laterally spreading tumors(LSTs)of the colorectum by computed tomography(CT)colonography(CTC).METHODS:Patients with LSTs measuring≥20 mm detected during colonoscopy were prospectively enrolled in the study.All patients underwent colonoscopy and subsequent CTC on the same day.CTC was performed using multi-detector CT without contrast in the prone and supine positions.Two radiologists blinded to the existence of LSTs read the virtual endoscopic images as well as 2-D images.LSTs were classified into granular and non-granular types based on colonoscopic appearance.RESULTS:Forty-seven pathologically proven LSTs were evaluated prospectively.Histology included adenomas in 19,mucosal cancers in 19 and T1 cancers in 9.The mean diameter of the LSTs was 35.1 mm.Twenty-eight(60%)LSTs were correctly identified by CTC,and the configuration was similar to the colonoscopic appearance in most cases.Detection rate for the granular type was significantly higher than that for the nongranular type(71%vs 31%,P=0.013).Detection rate of adenomas was significantly lower than mucosal cancers(32%vs 79%,P=0.008)and T1 cancers(32%vs 78%,P=0.042).CONCLUSION:The detection rate of LSTs by CTC,particularly the non-granular type was not acceptable.Practitioners should be aware of the relatively low detection rate when using CTC.
基金Supported by the National Cancer Institute,No.CA170357the Mayo Clinic Center for Cell Signaling in Gastroenterology,NIDDK Mo.P30DK084567
文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.