Long-term Use of Hormone Replacement Therapy is Associated With a Lower Risk of Developing High-risk Serrated Polyps in Women.

GOALS/BACKGROUND: Hormone replacement therapy (HRT) and parity have been suggested protective factors against the development of colorectal polyps. However, there are a limited number of studies that have examined the relationship of these factors with high-risk adenomatous polyps (HRAP) or high-risk serrated polyps (HRSP), which may have different causes and therefore implications for screening programs. STUDY: Data from a cross-sectional study of 1384 women undergoing screening-related colonoscopy between 2008 and 2016 were analyzed. Modified Poisson regression models with robust error variance were used to determine the relative risk of developing adenomatous polyps, serrated polyps, HRAPs, and HRSPs associated with pregnancy, menopausal status, and the use of HRT (duration and type). RESULTS: Women that used HRT for ≥6 years were at a significantly lower risk of developing a HRSP [risk ratios (RR): 0.53; 95% confidence interval (CI): 0.29-0.97]. Irrespective of the duration of use, the use of HRT that included progesterone alone or with estrogen was associated with a significantly lower risk of developing a HRSP (RR: 0.54; 95% CI: 0.30-0.95). The use HRT with progesterone for ≥6 years was associated with a nonsignificant lower risk of developing a HRSP (RR: 0.42; 95% CI: 0.17-1.04). None of the reproductive factors assessed or HRT were associated with the development of adenomatous polyps or HRAPs. CONCLUSIONS: The results of this study suggests that the long-term use of HRT, and therapies that include progesterone are associated with a lower risk of developing HRSPs. These results could have implications for targeted screening for serrated polyps among women.

A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps.

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of ß-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

Exploring polyps to colon carcinoma voyage: can blocking the crossroad halt the sequence?

Colorectal cancer is an important public health concern leading to significant cancer associate mortality. A vast majority of colon cancer arises from polyp which later follows adenoma, adenocarcinoma, and carcinoma sequence. This whole process takes several years to complete and recent genomic and proteomic technologies are identifying several targets involved in each step of polyp to carcinoma transformation in a large number of studies. Current text presents interaction network of targets involved in polyp to carcinoma transformation. In addition, important targets involved in each step according to network biological parameters are also presented. The functional overrepresentation analysis of each step targets and common top biological processes and pathways involved in carcinoma indicate several insights about this whole mechanism. Interaction networks indicate TP53, AKT1, GAPDH, INS, EGFR, and ALB as the most important targets commonly involved in polyp to carcinoma sequence. Though several important pathways are known to be involved in CRC, the central common involvement of PI3K-AKT indicates its potential for devising CRC management strategies. The common and central targets and pathways involved in polyp to carcinoma progression can shed light on its mechanism and potential management strategies. The data-driven approach aims to add valuable inputs to the mechanism of the years-long polyp-carcinoma sequence.

Vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

There is suggestive evidence for the role of vitamin D in the development of colorectal cancer (CRC). Due to high latitudes in Canada, many Canadians are vitamin D deficient throughout winter. In this analysis, we examined the association between vitamin D supplement use and high-risk adenomatous polyps (HRAPs). The study population was drawn from the biorepository at the Forzani & MacPhail Colon Cancer Screening Centre (CCSC) in Calgary. Individuals enrolled between 2013 and 2016 between the age of 50 and 74 years (n = 1409) were included. When examining the association between any supplemental vitamin D use and HRAPs, a protective effect is observed with an ORadj of 0.57 (95% CI: 0.33-0.96). Similarly, meeting the recommended daily intake (RDI) of vitamin D (600 IU) is protective against HRAPs with an ORadj of 0.78 (95% CI: 0.62-0.99). This study suggests that adequate vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

Circulating level of 25(OH)D3 with risk factors of asymptomatic adenoma and proximal non-adenoma colorectal polyps / Níveis circulantes de 25(OH)D3 com fatores de risco de adenoma assintomático e pólipos colorretais proximais sem adenoma

ABSTRACT Background: An inverse association between circulating vitamin D and adenoma risk hasbeen reported, but less is known about proximal inflammatory-hyperplastic polyps.Purpose: To investigate circulating 25(OH)D3and risk factors of proximal inflammatory-hyperplastic and adenoma colorectal polyps.Methods: From January 2017 to June 2019, consecutive asymptomatic average-risk partic-ipants undergoing initial screening colonoscopy. Questionnaires provided information oncolorectal polyp risk factors, and plasma samples were assayed for 25-Hydroxyvitamin-D ­25(OH)D3. The colorectal polyps were assessed, and medical history and demographic datawere obtained from each patient.Results: Of the 220 asymptomatic subjects, the prevalence of proximal inflammatory-hyperplastic polyps and adenoma polyps were 16.8%; 18.1% and 22.2%, respectively.Multivariate analysis revealed that low vitamin D (25(OH)D3< 18 ng/mL, OR = 3.94; 95%CI: 1.81­9.51) and current/former smoking (OR = 6.85; 95% CI: 2.98­15.70), high bodymass index (BMI > 24, OR = 5.32, 95% CI: 2.62­4.71) were independent predictors forproximal inflammatory-hyperplastic colorectal polyps (non-adenoma). Low vitamin D(25(OH)D3< 18 ng/mL, OR = 7.75; 95% CI: 3.19­18.80) and current/former smoking (OR = 3.75;95% CI: 1.30­10.81), age over 60 years old (OR = 2.38, 95% CI: 1.02­5.57), were independentpredictors for adenoma colorectal polyps.Conclusion: Low vitamin D and smoking are common risk factors for both adenomatous andproximal inflammatory hyperplastic polyps. Old age and BMI are additional risk factors forthe development of adenomatous and non-adenomatous colorectal polyps.

RESUMO Background: An inverse association between circulating vitamin D and adenoma risk hasbeen reported, but less is known about proximal inflammatory-hyperplastic polyps.Purpose: To investigate circulating 25(OH)D3and risk factors of proximal inflammatory-hyperplastic and adenoma colorectal polyps.Methods: From January 2017 to June 2019, consecutive asymptomatic average-risk partic-ipants undergoing initial screening colonoscopy. Questionnaires provided information oncolorectal polyp risk factors, and plasma samples were assayed for 25-Hydroxyvitamin-D ­25(OH)D3. The colorectal polyps were assessed, and medical history and demographic datawere obtained from each patient.Results: Of the 220 asymptomatic subjects, the prevalence of proximal inflammatory-hyperplastic polyps and adenoma polyps were 16.8%; 18.1% and 22.2%, respectively.Multivariate analysis revealed that low vitamin D (25(OH)D3< 18 ng/mL, OR = 3.94; 95%CI: 1.81­9.51) and current/former smoking (OR = 6.85; 95% CI: 2.98­15.70), high bodymass index (BMI > 24, OR = 5.32, 95% CI: 2.62­4.71) were independent predictors forproximal inflammatory-hyperplastic colorectal polyps (non-adenoma). Low vitamin D(25(OH)D3< 18 ng/mL, OR = 7.75; 95% CI: 3.19­18.80) and current/former smoking (OR = 3.75;95% CI: 1.30­10.81), age over 60 years old (OR = 2.38, 95% CI: 1.02­5.57), were independentpredictors for adenoma colorectal polyps.Conclusion: Low vitamin D and smoking are common risk factors for both adenomatous andproximal inflammatory hyperplastic polyps. Old age and BMI are additional risk factors forthe development of adenomatous and non-adenomatous colorectal polyps.

Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.

Celecoxib use and circulating oxylipins in a colon polyp prevention trial.

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P<0.05) and differences were greater among non-aspirin users. LOX derived 5- and 8-HETE were elevated with celecoxib and positively associated with systolic blood pressure (P = 0.011 and P = 0.019 respectively). 20-HETE, a prohypertensive androgen-sensitive CYP450 metabolite was higher with celecoxib absent aspirin and was positively associated with SBP in men (P = 0.040) but not women. Independent of celecoxib or aspirin, LOX derived metabolites from ARA were strongly associated with SBP including 5- and 8-HETE. These findings support oxylipins, particularly the ARA LOX-derived, in blood pressure control and indicate that pharmacologic inhibition of COX-2 has effects on LOX and CYP450 ARA metabolism that contribute to hypertension in some patients.

Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer.

BACKGROUND: There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. METHODS: A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. RESULTS: There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. CONCLUSIONS: Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.

Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas.

BACKGROUND: This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive. OBJECTIVES: To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention. SEARCH METHODS: We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016. SELECTION CRITERIA: We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable. MAIN RESULTS: We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution. AUTHORS' CONCLUSIONS: There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.

A healthy lifestyle index is associated with reduced risk of colorectal adenomatous polyps among non-users of non-steroidal anti-inflammatory drugs.

In a Columbia, South Carolina-based case-control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0-2) and healthy (3-5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95% CI 0.22, 1.29) and continuous (OR 0.75; 95% CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (p(interaction) = 0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72% lower odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95% CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53% (OR 0.47; 95% CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in non-users of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.

Colorectal cancer and adenomatous polyps in relation to allium vegetables intake: a meta-analysis of observational studies.

SCOPE: To provide updated quantitative estimates of the associations between allium vegetables intake and risk of colorectal cancer and colorectal adenomatous polyps. METHODS AND RESULTS: We combined all published data on the issue, using a meta-analytic approach. Pooled relative risks (RRs) were calculated using random-effects models. Sixteen studies (13 333 cases) were included in the meta-analyses of colorectal cancer. Seven studies provided information on garlic, six on onion, and four on total allium vegetables. The pooled RRs of colorectal cancer for the highest versus the lowest category of intake were 0.85 (95% confidence interval; CI, 0.72-1.00) for garlic (0.76 for case-control, 0.99 for cohort studies), 0.85 (95% CI, 0.70-1.04) for onion (0.74 for case-control, 1.04 for cohort studies), and 0.78 (95% CI, 0.56-1.08) for total allium vegetables. Significant heterogeneity was found for the three meta-analyses. The pooled RR of colorectal adenomatous polyps for the highest versus the lowest category of total allium vegetables intake was 0.88 (95% CI, 0.80-0.98, three studies), with no heterogeneity. CONCLUSION: High garlic intake may reduce the risk of colorectal cancer. However, evidence of such protection derived mainly from case-control studies. High intake of total allium vegetables may be associated with a risk reduction of colorectal adenomatous polyps.

[Early detection of bowel cancer in occupational surveillance examinations: switching from a guaiak-based to an immunochemical fecal occult blood test]. / Darmkrebsfrüherkennung im betriebsärztlichen Umfeld. Umstellung vom Guajak-basierten auf einen immunologischen Test auf okkultes Blut im Stuhl.

BACKGROUND: If the diagnosis is made early the cure rate of bowel cancer is more than 90 %. Occupational preventative medical care required by law and carried out by company physicians can be supplemented by a medical consultation and by simple screenings to interest employees in cancer prevention and refer them to registered general practitioners and specialist doctors for further diagnosis and treatment. SUBJECTS AND METHODS: Since 2001, BASF SE in Ludwigshafen, Germany offers its employees aged 45 and more a program to detect intestinal cancer early. The employees receive personal invitations for this program once a year. The participants answer a standard questionnaire about risk factors for bowel cancer and an endoscopic diagnosis, if this has already been carried out, and receive a FOBT. Since 2010 an immunological test system was used. We compare the results from two consecutive years with a Guajacum test system (g-FOBT) and an immunological test (i-FOBT). The German Association of Digestive and Metabolic Diseases, DGVS, recommends a colonoscopy if test results are positive or a family member has suffered from bowel cancer. RESULTS: Between 2008 and 2011, a total of 52,797 invitations were sent to employees aged 45 and over. Overall, 16,730 men (37.7 % of 46,245) and 1,585 women (24.4 % of 6,552) took part (in some cases more than once). The return rate of the FOBT increased from 66.7 % in 2008 to 79.5 % in 2011. Due to positive results and/or suspicious information in the questionnaire, 2,441 colonoscopies were recommended, 849 of them because of a positive FOBT. The medical department was informed of 224 endoscopy diagnoses. In 8 cases, manifested cancer (6 × colon, 2 × rectum) and in 57 cases adenomatous polyps were diagnosed as preliminary stages of cancer. Most of these diagnoses were made using the i-FOBT, the simultaneous increase in positive test results and therefore more frequent recommendations for a colonoscopy. CONCLUSION: The additional offer of a program for early detection of bowel cancer as part of an occupational surveillance examination helps detecting bowel cancer early in employees who show no symptoms. Since men on average fall ill earlier, it makes sense to offer these tests at the age of 45.  Personal invitations lead to consistently high participant rates and the simplicity of the i-FOBT leads to high return rates of tests. The rate of positive test results is higher compared to g-FOBT. In our follow-up, significantly more intestinal cancer and possible preliminary stages were detected through screening with the immunological test.

Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis.

Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APC)(Min/+) mice. Six-week-old wild-type and APC(Min/+) mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm) for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80-83%, P < .0001) total intestinal tumor multiplicity and size in APC(Min/+) mice (means ± SEM tumors for control vs GLAD were 67.1 ± 5.4 vs. 11.3 ± 1.1 in males and 72.3 ± 8.9 vs 14.5 ± 2.8 in females). Mice fed GLAD had >95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing ß-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APC(Min/+) mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.

Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial.

BACKGROUND: Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention. METHODS: To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 µg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group). RESULTS: After a median follow-up of 4 years (range 1-15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3% in the intervention and 64.5% in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39% reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95% CI 0.41-0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95% CI 0.37-0.99) and advanced adenomas (adjusted HR = 0.50; 95% CI 0.24-1.01). CONCLUSIONS: Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

Do antioxidants prevent colorectal cancer? A meta-analysis.

BACKGROUND: Oxidative stress is the first step involved in mutagenesis, carcinogenesis and aging. There has been great interest in recent years in potentially health benefits of dietary and antioxidant supplements in cancer prevention. OBJECTIVES: Our primary objectives were to estimate the global effect of antioxidants on colorectal cancer incidence, adenomatous polyp recurrence, overall mortality and cancer related mortality. A secondary aim was to evaluate these effects across specific antioxidant compounds, dose and duration of antioxidant supplementation. METHODS: Using Cochrane Collaboration methodology we searched for all randomized controlled trials (RCTs) from 1966 till May 2009 (MEDLINE, Cochrane Controlled Clinical Trials Registry), comparing antioxidant supplements with placebo or no intervention on the occurrence of colorectal cancer or adenoma. The results expressed as relative risk (RR) and 95% confidence intervals (95% CI) were obtained using random and fixed effect meta-analysis. RESULTS: Twenty RCTs, including 26 8590 participants, were eligible: 12 analyzing the colorectal cancer incidence included 25 0676 participants and 8 analyzing colorectal adenoma recurrence included 17914 participants. Antioxidant supplements had no significant effect on colorectal cancer incidence or colorectal adenoma recurrence (RR = 0. 94, 95% CI, 0.84-1.06, p = 0.32) in a random-effect meta-analysis. The antioxidant supplements had no significant effect on overall mortality (RR = 1.03, 95% CI, 0.99-1.07, p = 0.12) or cancer related mortality (RR = 1.05, 95% CI, 0.94-1.16, p = 0.38) in a random effect meta-analysis. Selenium supplementation was associated with a trend in reducing colorectal cancer incidence, (RR = 0.88, 95% CI, 0.55-1.40, p = 0.59), colorectal adenoma recurrence (RR = 0.70, 95% CI, 0.43-1.14, p = 0.16) and overall mortality (RR = 0.91, 95% CI, 0.82-1.02, p = 0.09). Beta carotene alone was associated with a slight increase in colorectal cancer incidence (RR = 1.09, 95% CI, 0.92-1.29, p = 0.34) and in combination with other antioxidants it was associated with an increase in mortality (RR = 1.05, 95% CI, 0.99-1.11, p = 0.10). For both selenium and beta carotene, the effect was not statistically significant. Vitamin C and Vitamin E combination slightly reduced colorectal cancer incidence with no effect on overall mortality. CONCLUSIONS: This meta-analysis found no evidence in favor of a protective effect of the studied antioxidant supplements in the prevention of colorectal cancer or cancer related mortality. Only selenium supplementation might have anticarcinogenic effects and requires further research.

Polipectomía colonoscópica y prevención a largo plazo de muertes por cáncer colorrectal / No disponible

Introducción: El National Polyp Study (NPS) mostró que la extracción colonoscópica de pólipos adenomatosos disminuyó la incidencia del cáncer colorrectal. Este estudio evalúa el efecto a largo plazo de la polipectomía colonoscópica sobre la mortalidad por cáncer colorrectal. Métodos: Se incluyó a todos los pacientes del NPS que se sometieron entre los años 1980 y 1990 a una colonoscopia en la que se demostró algún pólipo, adenomatoso o no. Se utilizó el National Death Index para evaluar la mortalidad total y sus causas en los pacientes incluidos. La mortalidad por cáncer colorrectal observada entre los pacientes con pólipos adenomatosos extirpados se comparó con la incidencia esperada de mortalidad por cáncer colorrectal en la población general y estimada por el Surveillance Epidemiology and End Results Program, y con la mortalidad observada en los pacientes con pólipos no adenomatosos. Resultados: Se les extirpó algún pólipo adenomatoso a 2.602 pacientes y fueron seguidos durante una mediana de 15,8 años; 1.246 fallecieron durante el período de seguimiento, 12 de ellos por cáncer colorrectal. En base a una estimación de 25,4 muertes esperadas por cáncer colorrectal en la población general, la tasa de mortalidad estandarizada fue de 0,47 (intervalo de confianza [IC] del 95%: 0,26-0,80; p=0,008) en los pacientes sometidos a una polipectomía colonoscópica, sugiriendo una reducción de la mortalidad del 53%. La mortalidad por cáncer colorrectal durante los primeros 10 años después de la polipectomía fue similar entre los pacientes con pólipos adenomatosos y aquellos con pólipos no adenomatosos (riesgo relativo: 1,2; IC del 95%: 0,1-10,6; p=0,1). Conclusiones: La extirpación colonoscópica de pólipos adenomatosos disminuye la muerte por cáncer colorrectal(AU)

Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer.

BACKGROUND: Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on the development of colorectal adenomas, the precursors of colorectal cancers, are not defined. AIMS: This study aimed to evaluate the potential effect of metformin on the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. METHODS: Among 488 consecutive diabetic patients who underwent colonoscopic surveillance after curative resection of colorectal cancer between 1998 and 2008, 240 patients were enrolled in this study and were compared in two groups: 114 patients taking metformin and 126 patients not taking metformin. Patient demographics, clinical characteristics, and colorectal adenoma incidence rate were analysed. RESULTS: After a median follow-up of 58 months, a total of 33 patients (28.9%) exhibited adenomatous colorectal polyps among the 114 patients who used metformin, compared with 58 (46.0%) patients with colorectal adenomas among the 126 patients who did not use metformin (odds ratio = 0.48, 95% confidence interval = 0.280-0.816, P = 0.008). After adjustment for clinically relevant factors, metformin use was found to be associated with a decreased incidence of colorectal adenomas (odds ratio = 0.27, 95% confidence interval = 0.100-0.758, P = 0.012) in diabetic patients with previous colorectal cancer. Metformin use in diabetic patients with previous colorectal cancer is associated with a lower risk of colorectal adenoma.

Colorectal cancer screening in LHU4 Chiavarese, Italy: ethical, methodological and outcome evaluations at the end of the first round.

UNLABELLED: INTRODUCTION. The screening programmes are very challenging from the ethical perspective, and their impact in terms of morbidity and mortality make secondary colorectal cancer prevention a valuable public health intervention. METHODS: The target population people aged 50-69 years receive an invitation card with a test-tube for the fecal occult blood test (FOBT) and an immunochemical test is used for fecal occult blood. Subjects positive to FOBT are invited to perform a gastroenterologic examination and a full colonoscopy. RESULTS: In the firt round of screening, 100% of the target population has been invited with an adhesion rate of 41.3%. A total of 1739 FOBT-positive subjects have been invited to the second level of the screening. 1429 of them have performed the gastroenterologic examination (83.9%). To date 956 full colonoscopies have been completed and the rate of subjects affected by carcinoma, malignant polyp and advanced adenoma has been equal to 23.5%. DISCUSSION: Thanks to the reminders already sent, an increasing compliance has been registered with an increased rate of subjects with a low schooling that have performed a FOBT test. With the aim to optimize all the operative aspects of the screening programme it is already ongoing a set of meetings between health workers of Local Health Unit 4 and General Practioners.

Dietary intake of PUFAs and colorectal polyp risk.

BACKGROUND: Marine-derived n-3 (omega-3) PUFAs may reduce risk of developing colorectal cancer; however, few studies have investigated the association of n-3 PUFA intakes on colorectal polyp risk. OBJECTIVE: The objective of this study was to examine the associations of dietary PUFA intake on risk of colorectal adenomatous and hyperplastic polyps. DESIGN: This was a colonoscopy-based case-control study that included 3166 polyp-free control subjects, 1597 adenomatous polyp cases, and 544 hyperplastic polyp cases. Dietary PUFA intake was calculated from food-frequency questionnaires and tested for association by using unconditional logistic regression. The urinary prostaglandin E(2) metabolite, which is a biomarker of prostaglandin E(2) production, was measured in 896 participants by using liquid chromatography and tandem mass spectrometry. RESULTS: n-6 PUFAs were not associated with adenomatous or hyperplastic polyps in either men or women. Marine-derived n-3 PUFAs were associated with reduced risk of colorectal adenomas in women only, with an adjusted OR of 0.67 (95% CI: 0.47, 0.97) for the highest quintile of intake compared with the lowest quintile of intake (P-trend = 0.01). Dietary intake of α-linolenic acid was associated with an increased risk of hyperplastic polyps in men (P-trend = 0.03), which was not seen in women. In women, but not in men, dietary intake of marine-derived n-3 PUFAs was negatively correlated with urinary prostaglandin E(2) production (r = -0.18; P = 0.002). CONCLUSION: Higher intakes of marine-derived n-3 PUFAs are associated with lower risk of adenomatous polyps in women, and the association may be mediated in part through a reduction in the production of prostaglandin E(2). This trial was registered at clinicaltrials.gov as NCT00625066.