Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies

AIM:To investigate the association between statin use and colorectal cancer risk,we conducted an updated meta-analysis of published studies.METHODS:We performed a comprehensive search for studies published up to July 2013.Eligible studies for this meta-analysis were either randomized controlled trials(RCTs)or observational studies(casecontrol or cohort)evaluating any exposure to statins and the risk of colorectal cancer.Two reviewers selected studies based on predefined inclusion criteria,and abstracted the data.Pooled relative risk(RR)estimates with their 95%CI were calculated using fixedand random-effects models.Then,we assessed the potential presence of publication bias and betweenstudies heterogeneity.To evaluate the results,we also performed a"leave-one-out"sensitivity analysis.RESULTS:A total of 40 studies,involving more than eight million subjects,contributed to the analysis.They were grouped on the basis of study design and,consequently,three separate meta-analyses were conducted.A similar modest reduction in the risk of colorectal cancer with statin use was observed,which was not statistically significant among RCTs(RR=0.89,95%CI:0.74-1.07;n=8),but reached statistical significance among cohort studies(RR=0.91,95%CI:0.83-1.00;n=13)and case-control studies(RR=0.92,95%CI:0.87-0.98;n=19).While we did not find significant evidence of selective outcome reporting or publication bias,substantial heterogeneity was detected,mainly among the observational studies.The sensitivity analysis confirmed the stability of our results.CONCLUSION:A modest reduction in risk of colorectal cancer among statin users cannot be disproved.Further targeted research is warranted.2014 Baishideng Publishing Group Co.,Limited.All rights     

Vitamin D receptor gene Tru9T polymorphism and risk for incidental sporadic colorectal adenomas

AIM: Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor (VDR). The aim of this study was polymorphism (Tru9I) in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study.METHODS: Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism.were associated with decreased risk for adenoma (OR,0.71; 95%CI, 0.40-1.25). The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile: the odds ratios (ORs) were, 0.51 (95%CI,0.21-1.24), 0.37 (95%CI, 0.11-1.28), 0.68 (95%CI, 0.33-1.41), and 0.36 (95%CI, 0.13-0.97) respectively. In joint/combined analyses, inverse associations were more obvious were younger (OR, 0.60; 95%CI, 0.26-1.37), women (OR,0.38; 95%CI, 0.17-0.88), did not smoke (OR, 0.39; 95%CI,0.13-1.23), or took NSAID (OR, 0.38; 95%CI, 0.12-1.25),but no evidence existed for interactions with calcium or vitamin D intake.CONCLUSION: Our findings suggest that the VDR Tru9Ipolymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.     

Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic colorectal adenomas

AIM: Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor (VDR). The aim of this study was to investigate whether a novel G (allele 'U')>A (allele 'u' polymorphism (Tru9I) in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study. METHODS: Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism. RESULTS: The frequencies of 'U' and 'u' alleles were 89.3% and 10.7%, respectively. The 'Uu' and 'uu' genotypes were associated with decreased risk for adenoma (OR, 0.71; 95%CI, 0.40-1.25). The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile: the odds ratios (ORs) were, 0.51 (95%CI, 0.21-1.24), 0.37 (95%CI, 0.11-1.28), 0.68 (95%CI, 0.33-1.41), and 0.36 (95%CI, 0.13-0.97) respectively. In joint/ combined analyses, inverse associations were more obvious among those who had at least one 'u' allele and also were younger (OR, 0.60; 95%CI, 0.26-1.37), women (OR, 0.38; 95%CI, 0.17-0.88), did not smoke (OR, 0.39; 95%CI, 0.13-1.23), or took NSAID (OR, 0.38; 95%CI, 0.12-1.25), but no evidence existed for interactions with calcium or vitamin D intake. CONCLUSION: Our findings suggest that the VDR Tru9I polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.     

他汀类药物预防结直肠肿瘤的Meta分析

目的系统评价他汀类药物对结直肠癌的发病率及病死率的影响。方法使用Medline等数据库收集他汀类药物与结直肠肿瘤相关的文献,筛选高质量文献,分别计算RR或OR值以及95%CI等,分析他汀类药物预防结直肠癌及结直肠腺瘤的作用,运用漏斗图评价发表偏倚。结果共纳入30项研究,研究对象2 417 713例。他汀类药物预防结直肠癌的森林图提示存在统计学差异(RR=0.87,95%CI:0.77-0.99,P=0.03),他汀类药物预防结直肠腺瘤的森林图不存在统计学差异(OR=0.61,95%CI:0.31-1.22,P=0.16),漏斗图分析各项研究未发现发表偏倚。结论他汀类药物对结直肠癌可能起到一定的化学预防作用,而对结直肠腺瘤的作用有待进一步研究。     

Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence

A traditional belief widespread across the biomedical community was that dietary habits and genetic predisposition were the basic factors causing colorectal cancer. In more recent times, however, a growing evidence has shown that other determinants can be very important in increasing (or reducing) incidence of this malignancy. The hypothesis that environmental and occupational risk factors are associated with colorectal cancer is gaining ground, and high risks of colorectal cancer have been reported among workers in some industrial branches. The aim of this study was to investigate the epidemiologic relationship between colorectal cancer and occupational exposures to several industrial activities, by means of a scientific literature review and meta-analysis. This work pointed out increased risks of colorectal cancer for labourers occupied in industries with a wide use of chemical compounds, such as leather (RR = 1.70, 95%CI: 1.24-2.34), basic metals (RR = 1.32, 95%CI: 1.07-1.65), plastic and rubber manufacturing (RR = 1.30, 95%CI: 0.98-1.71 and RR = 1.27, 95%CI: 0.92-1.76, respectively), besides workers in the sector of repair and installation of machinery exposed to asbestos (RR = 1.40, 95%CI: 1.07-1.84). Based on our results, the estimated crude excess risk fraction attributable to occupational exposure ranged from about 11% to about 15%. However, homogeneous pattern of association between colorectal cancer and industrial branches did not emerge from this review.     

Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population

AIM: To investigate prevalence and risk factors for colorectal neoplasms in adults aged 50 years, for whom screening is not recommended.METHODS: This cross-sectional study compared prevalence and characteristics of colorectal and advanced adenomas in patients aged 50 years who underwent colonoscopy screening with subjects aged ≥ 50 years. To evaluate risk factors for colorectal and advanced adenoma in young adults, we used multivariable logistic regression models. Colorectal neoplasm characteristics were evaluated and compared with those in older patients.RESULTS: Among 2819 patients included, prevalences of colorectal adenoma and advanced adenoma were 19.7% and 1.5%, respectively. As patient age increased, so did the prevalence of colorectal neoplasm. However, prevalence of advanced adenoma did not differ between age-groups 45-49 years and ≥ 50 years(OR = 0.43, 95%CI: 0.17-1.07, P = 0.070). In younger age-group( 50 years), colorectal adenoma was significantly associated with older age, waist circumference(OR = 1.72, 95%CI: 1.15-2.55, P = 0.008), and current smoking(OR = 1.60, 95%CI: 1.07-2.41, P = 0.023). Alcohol consumption was an independent risk factor for colorectal advanced adenoma(OR = 3.69, 95%CI: 1.08-12.54, P = 0.037). Multiple neoplasms and large neoplasms(≥ 1 cm) were more prevalent in subjects ≥ 50 years.CONCLUSION: Current screening strategies for colorectal cancer may need to be amended to account for patient age, especially in young subjects with abdominal obesity, current smoking and alcohol consumption.     

Fat, fiber, meat and the risk of colorectal adenomas

OBJECTIVE: The aim of this study was to determine the relationship between fat, fiber, and meat intake, and risk of colorectal adenoma recurrence. METHODS: We determined adenoma recurrence and dietary intake for 1,520 participants in two randomized trials: The Antioxidant Polyp Prevention Study and Calcium Polyp Prevention Study. Subjects underwent baseline colonoscopy with removal of all adenomas, and dietary intake was estimated with a validated semiquantitative food frequency questionnaire. Follow-up colonoscopy was performed 1 and 4 yr later. Pooled risk ratios for adenoma recurrence were obtained by generalized linear regression, with adjustment for age, sex, clinical center, treatment category, study, and duration of observation. RESULTS: In the total colorectum, fiber intake was weakly and nonsignificantly associated with a risk for all adenomas (RR quartile 4 vs quartile 1=0.85, 95% CI 0.69-1.05) and advanced adenomas (RR=0.88, 95% CI 0.54-1.44). Associations were stronger for adenomas in the proximal colon (RR=0.73, 95% CI 0.56-0.97) and some fiber subtypes (fruit and vegetable, grain). There was no association between fat or total red meat intake and risk of adenoma or advanced adenoma recurrence. However, when considering other meats, risk (quartile 4 vs quartile 1) for advanced adenoma was increased for processed meat (RR=1.75, 95% CI 1.02-2.99) and decreased for chicken (RR=0.61, 95% CI 0.38-0.98). CONCLUSION: The inverse associations between fiber intake and risk of adenoma recurrence we observed are weak, and not statistically significant. Our data indicate that intake of specific meats may have different effects on risk.     

Consumption of garlic and risk of colorectal cancer: An updated meta-analysis of prospective studies

AIM: To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer.METHODS: Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies.RESULTS: A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59).CONCLUSION: Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk.     

Endoscopic mucosal resection of colorectal adenomas>20mm:Risk factors for recurrence

AIM: To evaluate risk factors for local recurrence after endoscopic mucosal resection of colorectal adenomas 20 mm.METHODS: Retrospective data analysis of 216 endoscopic mucosal resections for colorectal adenomas 20 mm in 179 patients(40.3% female; median age 68 years; range 35-91 years). All patients had at least 1 follow-up endoscopy with a minimum control interval of 2 mo(mean follow-up 6 mo/2.0-43.4 mo). Possible factors associated with local recurrence were analyzed by univariate and multivariate analysis. RESULTS: Median size of the lesions was 30 mm(20-70 mm),69.0% were localized in the right-sided(cecum,ascending and transverse) colon. Most of the lesions(85.6%) showed a non-pedunculated morphology and the majority of resections was in piecemeal technique(78.7%). Histology showed carcinoma or high-grade intraepithelial neoplasia in 51/216(23.6%) lesions including 4 low risk carcinomas(pT1 a,L0,V0,R0- G1/G2). Histologically proven recurrence was observed in 33/216 patients(15.3%). Patient age65 years,polyp size30 mm,non-pedunculated morphology,localization in the right-sided colon,piecemeal resection and tubular-villous histology were found as associated factors in univariate analysis. On multivariate analysis,only localization in the rightsided colon(HR = 6.842/95%CI:1.540-30.394; P=0.011),tubular-villous histology(HR = 3.713/95%CI: 1.617-8.528;P=0.002) and polyp size30 mm(HR=2.563/95%CI:1.179-5.570; P=0.017) were significantly associated risk factors for adenoma recurrence. CONCLUSION: Meticulous endoscopic follow-up is warranted after endoscopic mucosal resection of adenomas localized in the right-sided colon larger than 30 mm,with tubular-villous histology.     

IFOBT与肿瘤标志物、炎症指标联合检测对结直肠进展期腺瘤发生的预测价值

背景目前临床缺乏对结直肠癌前病变有效的无创筛查手段,识别高危人群和多指标联合检测已成为癌及癌前病变筛查的趋势.多种炎症指标已广泛用于各种肿瘤的诊断及预后,而对癌前病变诊断价值的研究较少.目的探讨粪便免疫潜血实验(immunochemical fecal occult blood testing,IFOBT),肿瘤标志物(CEA、CA199),炎症指标包括中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)、血小板/淋巴细胞比值(platelet/lymphocyte ratio,PLR)及一般临床特征对结直肠进展期腺瘤息肉发生的预测价值.方法回顾性分析我院2014-2018年行电子结肠镜检查并经病理学证实的295例结直肠进展期腺瘤病例作为观察组,选择同期448例非进展期腺瘤病例作为对照组,收集患者的一般临床资料包括基本特征(性别、年龄)、生活习惯(吸烟史、饮酒史)、既往史(高血压史、冠心病史、糖尿病史),手术史(胆囊或阑尾切除史);实验室检查(NLR、PLR、CEA、CA199、IFOBT);进行单因素差异分析,将有意义的结果纳入二元logistic回归分析,绘制ROC曲线,评估相关指标对结直肠进展期腺瘤发生的预测价值.结果Logistic回归分析显示:年龄(OR=1.047,95%CI:1.028-1.066,P=0.000)、吸烟(OR=1.880,95%CI:1.250-2.826,P=0.002)、糖尿病(OR=2.073,95CI%:1.216-3.535,P=0.007)、既往胆囊切除(OR=9.206,95CI%:2.904-29.181,P=0.000)、IFOBT(OR=7.681,95%CI:4.585-12.869,P=0.000)、CA199(OR=1.039,95%CI:1.018-1.059,P=0.000)、NLR(OR=1.706,95%CI:1.388-2.097,P=0.000)与进展期腺瘤的发生独立相关.对于预测进展期腺瘤的发生,IFOBT的灵敏度为34.6%,特异度为94.2%,AUC为0.644,95%CI:0.602-0.686,CA199的最佳截断点为7.87 U/mL,灵敏度为53.9%,特异度为66.1%,AUC为0.639,95%CI:0.598-0.679,NLR的最佳截断点为2.04,灵敏度为50.2%.特异度为71.8%,AUC为0.645,95%CI:0.605-0.685,当三者联合检测时其灵敏度为52.9%,特异度为82.8%,AUC 95%CI为0.752(0.716-0.788),进展期腺瘤亚组分析中,IFOBT(-)和IFOBT(+)亚组之间的腺瘤位置(P=0.048)、腺瘤直径(P=0.000)、分化级别(P=0.000)差异有统计学意义,低NLR(<2.04)和高NLR(≥2.04)亚组之间的性别(P=0.004)、腺瘤直径(P=0.028)、分化级别(P=0.000)差异有统计学意义.结论高龄、吸烟、糖尿病、既往胆囊切除人群更易发生结直肠进展期腺瘤,临床需对此类人群提高重视,IFOBT、NLR、CA199对进展期腺瘤的发生具有诊断意义,三者联合检测时其诊断效能最佳.     

Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: A meta-analysis

AIM: To conduct a systematic review and meta-analysis of published population-based randomized controlled trials (RCTs).METHODS: RCTs evaluating the difference in mortality and incidence of colorectal cancer (CRC) between a screening flexible sigmoidoscopy (FS) group and control group (not assigned to screening FS) with a minimum 5 years median follow-up were identified by a search of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled Trials through August 2013. Random effects model was used for meta-analysis.RESULTS: Four RCTs with a total of 165659 patients in the FS group and 249707 patients in the control group were included in meta-analysis. Intention-to-treat analysis showed that there was a 22% risk reduction in total incidence of CRC (RR = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63-0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR = 0.57, 95%CI: 0.45-0.72).CONCLUSION: This meta-analysis suggests that screening FS can reduce the incidence of proximal and distal CRC and mortality from distal CRC along with reduction in diagnosis of advanced CRC.     

Circulating levels of vitamin D and colorectal adenoma: A case-control study and a meta-analysis

AIM: To examine the association between circulating 25-hydroxyvitamin D [25(OH)D] levels and colorectal adenoma in a case-control study and a meta-analysis. METHODS: We conducted a matched case-control study(112 cases and 112 matched controls) and combined 15 studies, including our study, in a metaanalysis. The study-specific odds ratios(ORs) and 95% confidence intervals(CIs) were pooled using a randomeffects model. In total, 5454 colorectal adenomas and 6656 controls were included in the meta-analysis. RESULTS: In a meta-analysis including 14 previous studies and our study, we observed a significant inverse association between circulating 25(OH)D levels and colorectal adenoma(OR = 0.68; 95%CI: 0.54-0.82) when comparing the highest category with the lowest category. Stratification by adenoma location(proximal or distal adenoma) showed similar estimates. When we stratified by study region, the ORs(95%CIs) were 0.70(0.52-0.88) in the US and 0.66(0.34-0.97) in Asia. CONCLUSION: These data suggest an inverse association between circulating 25(OH) Dlevels and colorectal adenoma in both Western and Asian populations.     

Accuracy of early detection of colorectal tumours by stool methylation markers: A meta-analysis

AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours.METHODS: Electronic databases including PubMed, Web of Science, Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool (QADAS) was used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis.RESULTS: Thirty-seven articles met the inclusion criteria, and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer (CRC) were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. For adenoma, the sensitivity and specificity were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic OR was 47.57 (95%CI: 20.08-112.72), the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: sensitivity was 43% (95%CI: 38%-49%), specificity was 94% (95%CI: 91%-97%), the diagnostic OR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563.CONCLUSION: Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis.     

Helicobacter pylori infection concomitant with metabolic syndrome further increase risk of colorectal adenomas

AIM: To investigate the association of colorectal adenomas with both Helicobacter pylori (H. pylori) infection and metabolic syndrome. METHODS: Using a cross-sectional hospital-based study, we analyzed physical examination data from 9311 healthy subjects with overnight physical examinations performed between January 2004 and December 2006. Examined data included gender, age, life style, anthropometric measurements, blood pressure, biochemical and hematological studies, H. pylori infection detected by esophagogastroduodenoscopy and biopsy urease tests, and colorectal adenomas detected with a complete total colonoscopy. RESULTS: The prevalence values for H. pylori infection, metabolic syndrome, and colorectal adenoma were39.2%, 18.7%, and 20.7%, respectively. Colorectal adenoma risk factors included male gender [odd ratio (OR): 2.005, 95% conf idence interval (CI): 1.740-2.310, P < 0.001], advanced age (OR: 1.046, 95% CI: 1.040-1.052, P < 0.001), smoking (OR: 1.377, 95% CI: 1.146-1.654, P = 0.001), increased body fat (OR: 1.016, 95% CI: 1.007-1.026, P = 0.001), higher white blood cell count (OR: 1.038, 95% CI: 1.005-1.073, P = 0.025), H. pylori infection (OR: 1.366, 95% CI: 1.230-1.517, P < 0.001), and metabolic syndrome (OR: 1.408, 95% CI: 1.231-1.610, P < 0.001). In addition, concomitant H. pylori infection with metabolic syndrome further increased the probability of colorectal adenomas. CONCLUSION: Our study revealed H. pylori infection with concomitant metabolic syndrome might further increase the risk of colorectal adenomas.     

Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies

AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-a) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios(ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTS A total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, P heterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma(OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, P heterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-a and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI: 0.92-1.55).CONCLUSION Summary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas

BACKGROUND & AIMS: In human and animal studies, nonsteroidal anti-inflammatory drugs have been associated with a reduced risk of colorectal neoplasia. Although the underlying mechanisms are unknown, inhibition of cyclooxygenase (COX), particularly COX-2, is thought to play a role. We conducted a randomized, placebo-controlled, double-blind trial to assess whether use of the selective COX-2 inhibitor rofecoxib would reduce the risk of colorectal adenomas. METHODS: We randomized 2587 subjects with a recent history of histologically confirmed adenomas to receive daily placebo or 25 mg rofecoxib. Randomization was stratified by baseline use of cardioprotective aspirin. Colonoscopic follow-up evaluation was planned for 1 and 3 years after randomization. The primary end point was all adenomas diagnosed during 3 years' treatment. In a modified intent-to-treat analysis, we computed the relative risk of any adenoma after randomization, using Mantel-Haenszel statistics stratified by low-dose aspirin use at baseline. RESULTS: Adenoma recurrence was less frequent for rofecoxib subjects than for those randomized to placebo (41% vs 55%; P < .0001; relative risk [RR], 0.76; 95% confidence interval [CI], 0.69-0.83). Rofecoxib also conferred a reduction in risk of advanced adenomas (P < .01). The chemopreventive effect was more pronounced in the first year (RR, 0.65; 95% CI, 0.57-0.73) than in the subsequent 2 years (RR, 0.81; 95% CI, 0.71-0.93). As reported previously, rofecoxib was associated with increased risks of significant upper gastrointestinal events and serious thrombotic cardiovascular events. CONCLUSIONS: In this randomized trial, rofecoxib significantly reduced the risk of colorectal adenomas, but also had serious toxicity.     

血脂异常患者结直肠早期癌发病的危险因素分析

探讨血脂异常患者结直肠早期癌发病的危险因素,以及他汀类药物在其中可能发挥的作用。回顾性分析2018年2月—2021年2月北京友谊医院消化科行内镜治疗合并血脂异常的结直肠肿物患者资料。根据结肠镜及病理结果将266例患者分为结直肠腺瘤组（n=174）和结直肠早期癌组（n=92）。分析两组患者临床资料的差异,采用Logistic回归分析血脂异常患者结直肠早期癌发病的危险因素。结果发现,与结直肠腺瘤组相比,结直肠早期癌组患者的男性比例（64.1%比25.9%）、吸烟比例（41.3%比14.4%）和饮酒比例（37.0% 比17.2%）更高,同时低密度脂蛋白胆固醇［（3.06±0.81） mmol/L比（2.60±0.74） mmol/L］和总胆固醇值更高［（5.27±1.22） mmol/L 比（4.61±1.06） mmol/L］,而他汀用药占比更低（27.2% 比52.9%）,差异均有统计学意义（P均<0.05）。多因素Logistic回归分析显示,男性（OR=3.641, 95%CI：1.694~7.826）、吸烟（OR=2.920, 95%CI：1.159~7.356）以及较高的低密度脂蛋白胆固醇（OR=2.203,95%CI：1.481~3.277）、较高的总胆固醇水平（OR=1.744,95%CI：1.329~2.289）是血脂异常患者结直肠早期癌发生的危险因素,而他汀用药史（OR=0.469,95%CI：0.236~0.932）对避免血脂异常患者结直肠早期癌的发生具有保护作用。应对血脂异常患者进行戒烟宣教,监测低密度脂蛋白胆固醇、总胆固醇水平,必要时使用他汀类药物促进血脂达标,同时积极进行结直肠癌的早期筛查。     

Cyclooxygenase-2 Expression in Colorectal Adenomas

PURPOSE: Cyclooxygenase-2 is an important target for nonsteroidal anti-inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase-2 expression in adenomas with other adenoma characteristics. METHODS: Cyclooxygenase-2 expression was evaluated immunohistochemically in 95 endoscopically resected colorectal adenomas. RESULTS: Cyclooxygenase-2 was expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74 percent (70/95) of adenomas. Expression was related significantly to grade of dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic regression analysis showed cyclooxygenase-2 expression in adenoma cells to be independently associated with grade of dysplasia (P = 0.001). CONCLUSION: Observed associations suggest that cyclooxygenase-2 plays an important role in progression of the adenoma-to-carcinoma sequence.     

Colorectal Adenoma Characteristics as Predictors of Recurrence

PURPOSE The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians. This study was designed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence.METHODS The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial. At both baseline and three-year examinations, the characteristics of adenomas were recorded according to a standardized protocol. The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia), and proximal and distal recurrence.RESULTS A three-year recurrence was observed in 122 patients (22.1 percent), and more than one-half of them had recurrent adenomas on the proximal colon. After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence. In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence (5.3; 95 percent confidence interval, 2.7–10.3), proximal recurrence (8.5; 95 percent confidence interval, 4.1–18), and advanced adenoma recurrence (5.5; 95 percent confidence interval, 2.4–12.6).CONCLUSIONS Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon. The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas.Other Investigators in the Study Group are listed in Appendix 1.Supported by the Europe Against Cancer Programme, the Association Contre le Cancer (Brussels), the Association Luxembourgeoise Contre le Cancer, INSERM (France, grant 91-1002), the French Ministry of Health (PHRC), the Deutsches Krebsforschungzentrum, the Danish Cancer Society, the FISS (Spain), Hospital Supplies (Ireland), the University of Coimbra (Portugal), and Istituto Tumori Genova (Italy). The calcium and its placebo treatment were provided by Sandoz France. The fiber and its placebo treatment were provided by Reckitt and Coleman (United Kingdom).