The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

AIM: Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. METHOD: This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. RESULTS: Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. CONCLUSION: Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

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.

Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.

BACKGROUND & AIMS: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.

PPV and Detection Rate of mt-sDNA Testing, FIT, and CT Colonography for Advanced Neoplasia: A Hierarchic Bayesian Meta-Analysis of the Noninvasive Colorectal Screening Tests.

BACKGROUND. Noninvasive tests for colorectal cancer (CRC) screening and prevention limit the need for invasive colonoscopy to follow up positive test results. However, the relative performance characteristics of available noninvasive tests have not yet been adequately compared. OBJECTIVE. We performed a systematic review and meta-analysis to compare the diagnostic performance of the available noninvasive CRC screening tests, including multitarget stool DNA (mt-sDNA) testing, fecal immunochemical testing (FIT), and CT colonography (CTC), with an emphasis on comparison of PPV and detection rate (DR) for advanced neoplasia (AN; encompassing cases of advanced adenomas and CRC). EVIDENCE ACQUISITION. After systematic searches of MEDLINE and Google Scholar databases, 10 mt-sDNA, 27 CTC, and 88 FIT published screening studies involving 25,132, 33,493, and 2,355,958 asymptomatic adults, respectively, were included. Meta-analysis with hierarchic Bayesian modeling was conducted in accordance with Cochrane Collaboration and PRISMA guidelines to determine test positivity rates (TPRs) leading to optical colonoscopy, as well as PPVs and DRs for both AN and CRC. Different positivity thresholds were considered for FIT and CTC. EVIDENCE SYNTHESIS. Point estimates (with 95% credible intervals) from pooled Bayesian meta-analysis combining all thresholds for FIT and stratifying CTC results by a polyp size threshold of 6 mm or larger (CTC6) and 10 mm or larger (CTC10) were calculated. TPR was 13.5% (10.9-16.6%) for mt-sDNA testing, 6.4% (5.8-7.2%) for FIT, 13.4% (11.4-15.6%) for CTC6, and 6.6% (5.2-7.7%) for CTC10. AN PPV was 26.9% (95% credible interval, 21.8-33.2%) for mt-sDNA testing, 31.8% (29.3-34.5%) for FIT, 34.4% (27.2-41.0%) for CTC6, and 61.0% (54.0-70.0%) for CTC10. CRC PPV was 2.4% (1.5-3.9%) for mt-sDNA testing, 4.9% (4.3-5.3%) for FIT, 3.5% (2.5-4.8%) for CTC6, and 6.0% (4.3-8.0%) for CTC10. The DR for AN was 3.4% (95% credible interval, 2.5-4.8%) for mt-SDNA, 2.0% (1.8-2.3%) for FIT, 4.8% (4.0-6.5%) for CTC6, and 4.0% (3.0-4.6%) for CTC10. When FIT is restricted to a lower threshold (< 10 µg Hb/g feces), its performance profile is similar to that of mt-sDNA testing, although available data are limited. AN PPV odds ratios (relative to CTC10 as the reference) were 0.24 (95% credible interval, 0.17-0.33) for mt-sDNA testing, 0.30 (0.24-0.45) for FIT, and 0.33 (0.25-0.47) for CTC6. CONCLUSION. Among noninvasive CRC screening tests, CTC with a polyp size threshold of 10 mm or larger most effectively targets AN, preserving detection while also decreasing unnecessary colonoscopies compared with mt-sDNA testing and FIT. CLINICAL IMPACT. CTC performed with a polyp size threshold for colonoscopy referral set at 10 mm or larger represents the most effective and efficient noninvasive screening test for CRC prevention and detection.

Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study.

CONTEXT: Colonic polyps occur in 30-40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. OBJECTIVE: Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. DESIGN: Exploratory cross-sectional study in two tertiary Italian referral centres. MET: hods: Out of 153 acromegalic patients, we selected 58 patients (36-82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. RESULTS: An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). CONCLUSIONS: These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.

Optimization of Erlotinib Plus Sulindac Dosing Regimens for Intestinal Cancer Prevention in an Apc-Mutant Model of Familial Adenomatous Polyposis (FAP).

A clinical trial in patients with familial adenomatous polyposis (FAP) demonstrated that sulindac plus erlotinib (SUL+ERL) had good efficacy in the duodenum and colon, but toxicity issues raised concerns for long-term prevention. We performed a biomarker study in the polyposis in rat colon (Pirc) model, observing phosphorylated Erk inhibition in colon polyps for up to 10 days after discontinuing ERL+SUL administration. In a follow-up study lasting 16 weeks, significant reduction of colon and small intestine (SI) tumor burden was detected, especially in rats given 250 ppm SUL in the diet plus once-a-week intragastric dosing of ERL at 21 or 42 mg/kg body weight (BW). A long-term study further demonstrated antitumor efficacy in the colon and SI at 52 weeks, when 250 ppm SUL was combined with once-a-week intragastric administration of ERL at 10, 21, or 42 mg/kg BW. Tumor-associated matrix metalloproteinase-7 (Mmp7), tumor necrosis factor (Tnf), and early growth response 1 (Egr1) were decreased at 16 weeks by ERL+SUL, and this was sustained in the long-term study for Mmp7 and Tnf. Based on the collective results, the optimal dose combination of ERL 10 mg/kg BW plus 250 ppm SUL lacked toxicity, inhibited molecular biomarkers, and exhibited effective antitumor activity. We conclude that switching from continuous to once-per-week ERL, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care SUL against adenomatous polyps in the colon and SI, with clinical relevance for patients with FAP before or after colectomy. PREVENTION RELEVANCE: This investigation concludes that switching from continuous to once-per-week erlotinib, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care sulindac against adenomatous polyps in the colon and small intestine, with clinical relevance for patients with FAP before or after colectomy.

No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial.

BACKGROUND & AIMS: The effects of vitamin D on risk of colorectal cancer precursors are not clear. We examined the influence of vitamin D supplementation on risk of colorectal adenomas and serrated polyps in a prespecified ancillary study of a large-scale prevention trial (the vitamin D and omegA-3 trial, VITAL) of individuals who were free of cancer and cardiovascular disease at enrollment. METHODS: In VITAL trial, 25,871 adults with no history of cancer or cardiovascular disease (12,786 men 50 years or older and 13,085 women 55 years or older) were randomly assigned to groups given daily dietary supplements (2000 IU vitamin D3 and 1 g marine n-3 fatty acid) or placebo. Patients were assigned to groups from November 2011 through March 2014 and the study ended on December 31, 2017. We confirmed conventional adenomas and serrated polyps by reviewing histopathology reports from participants who had reported a diagnosis of polyps and were asked by their doctors to return for a repeat colonoscopy or sigmoidoscopy in 5 years or less. We calculated the odds ratios (ORs) and 95% CIs by logistic regression, after adjusting for age, sex, n-3 treatment assignment, and history of endoscopy at time of randomization. RESULTS: During a median follow-up of 5.3 years, we documented 308 cases of conventional adenomas in 12,927 participants in the vitamin D group and 287 cases in 12,944 participants in the placebo group (OR for the association of vitamin D supplementation with adenoma, 1.08; 95% CI, 0.92-1.27). There were 172 cases of serrated polyps in the vitamin D group and 169 cases in the placebo group (OR for the association of vitamin D supplementation with serrated polyp, 1.02; 95% CI, 0.82-1.26). Supplementation was not associated with polyp size, location, multiplicity, or histologic features. We found evidence for an interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D, measured in 15,787 participants at randomization. Among individuals with serum levels of 25-hydroxyvitamin D below 30 ng/mL, the OR associated with supplementation for conventional adenoma was 0.82 (95% CI, 0.60-1.13), whereas among individuals with serum levels of 25-hydroxyvitamin D above 30 ng/mL, the OR for conventional adenoma was 1.20 (95% CI, 0.92-1.55) (P for interaction = .07). There was a significant interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D in their association with advanced adenoma (P for interaction = .04). CONCLUSIONS: Based on an ancillary study of data from the VITAL trial, daily vitamin D supplementation (2000 IU) was not associated with risk of colorectal cancer precursors in average-risk adults not selected for vitamin D insufficiency. A potential benefit for individuals with low baseline level of vitamin D requires further investigation. ClinicalTrials.gov number: NCT01169259.

[Efficacy and safety of lyophilized concentrate purple corn (Zea mays L.) in preventing the formation of colonic polyps]. / Eficacia y seguridad del concentrado liofilizado de Zea mays morado en la prevención de formación de pólipos colónicos.

INTRODUCTION: Colorectal cancer (CRC) is a worldwide problem of public health and arises mainly from polyps. In last 25 years, a strategy called chemoprevention that consists of food intake like purple corn and turmeric or chemical substances like acetyl salicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) that prevent effectively carcinogenesis reducing the risk of polyp development. OBJECTIVE: To determine the efficacy and safety of lyophilized concentrate of purple corn (Zea mays L.) 200 mg in the prevention of colonic polyps development in private gastroenterological practice Methods: we randomly assigned 112 patients (cases) to receive this product and 112 patients (controls) to receive placebo, during 3 years. Both groups had similar demographic, clinical and medical history characteristics. RESULTS: we found that cases developed 83% less polyps than controls (p <0.001). The cases that developed polyps were smaller in number, size and histology than at the beginning of the trial. The adverse events that cases presented were 4.5% similar to controls, mainly petechiae. CONCLUSION: We conclude that the lyophilized concentrate of purple corn (Zea mays L.) 200 mg was effective and safe in preventing the developmentof colonic polyps.

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.

A healthy lifestyle pattern has a protective association with colorectal polyps.

BACKGROUND: Colorectal cancer is associated with lifestyle characteristics such as diet, physical inactivity, obesity, and smoking, but these are not incorporated in screening recommendations. Moreover, the joint association of these factors with various colorectal polyps is not established. METHODS: A case-control study, among consecutive subjects aged 40-70 years, undergoing colonoscopy. Cases with colorectal polyps were compared with controls. Detailed information was gathered regarding polyp histology and anatomic location, demographics, medical history, anthropometrics, and lifestyle. The healthy lifestyle index was estimated as the sum of: non-smoking, maintaining a healthy weight, healthy diet, and physical activity. RESULTS: A total of 788 participants were included (cases n = 403, controls n = 385). The healthy lifestyle index had a negative association with colorectal polyps (OR = 0.72, 95% CI 0.62-0.85, P < 0.001), both adenomas and serrated polyps (OR = 0.75, 0.64-0.89, and OR = 0.59, 0.44-0.79, respectively), and both proximal and distal adenomas (OR = 0.77, 0.62-0.95, and OR = 0.73, 0.59-0.90, respectively). Adherence to ≥ 2 healthy lifestyle components was strongly related with colorectal polyps (OR = 0.50, 0.34-0.75, P = 0.001). Abstinence from smoking, and a healthy diet were the factors most strongly associated with lower odds of colorectal polyps (OR = 0.58, 0.42-0.79, and OR = 0.61, 0.44-0.85, respectively). CONCLUSIONS: Adherence to a healthy lifestyle (≥2 healthy lifestyle components) is inversely associated with colorectal polyps, especially serrated and distal polyps, with no dose-response association. Components most strongly associated with lower odds of colorectal polyps were maintaining a healthy diet and abstinence from smoking. Lifestyle-related characteristics may assist in risk stratification and are potential goals for colorectal neoplasia prevention.

The BE GONE trial study protocol: a randomized crossover dietary intervention of dry beans targeting the gut microbiome of overweight and obese patients with a history of colorectal polyps or cancer.

BACKGROUND: Mouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity's Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk. METHODS/DESIGN: This randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant's usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome. DISCUSSION: The BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases. TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.

Potencial efeito preventivo do Lactobacillus acidophilus e Lactobacillus plantarum em pacientes com pólipos ou câncer colorretal / Potential preventive effect of lactobacillus acidophilus and lactobacillus plantarum in patients with polyps or colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.

RESUMO CONTEXTO: O câncer colorretal é uma das principais causas de morte em todo o mundo. Muitos estudos têm sido feitos sobre a biologia de sua formação, bem como o seu tratamento nos últimos anos. Um dos fatores envolvidos na formação ou no tratamento desta malignidade pode ser atribuído à flora microbiana no intestino. OBJETIVO: Este estudo investigou o potencial efeito preventivo de Lactobacillus acidophilus e Lactobacillus plantarum em pacientes com pólipos ou câncer colorretal (CCR). MÉTODOS: Um total de 77 amostras foram selecionadas e três grupos foram formados, a saber, indivíduos portadores de CCR, pólipos e indivíduos saudáveis. O DNA genomico de espécimes fecais e de amostras padrão foi extraído e amplificado empregando primers que focalizaram o gene do rRNA 16S para a deteção inicial. A quantificação do PCR em tempo real absoluto foi utilizada para determinar a cópia da expressão bacteriana por grama de fezes. RESULTADOS: Não foram observadas diferenças significativas entre idade e sexo nos grupos citados (P=0,06). O número médio de cópias de Lactobacillus acidophilus mostra diferença significativa entre o grupo saudável e aqueles com pólipos (P<0,0001), o grupo saudável e aqueles com câncer colorretal (P<0,0001), bem como aqueles com pólipos e câncer colorretal pacientes (P<0,0001). CONCLUSÃO: Estes resultados podem indicar que a ingestão de Lactobacillus acidophilus em pessoas com antecedentes familiares de CCR e pessoas com pólipos pode ser uma forma de prevenir, tratar ou reduzir a gravidade da CCR.

Mediterranean dietary components are inversely associated with advanced colorectal polyps: A case-control study.

AIM: To evaluate the association between the Mediterranean diet (MD) pattern and its components, and advanced colorectal polyps (adenoma and serrated adenoma). METHODS: A case-control study among patients undergoing screening, diagnostic or surveillance colonoscopies during 2010-2015 at the Tel-Aviv Medical Center, Gastroenterology Department. Cases with advanced polyps were defined as: Advanced adenoma [> 10 mm, with features of high grade dysplasia (HGD) or villous histology], advanced serrated adenoma (> 10 mm or with dysplasia) or multiple (≥ 3) non-advanced adenomas or serrated adenomas. Cases of non-advanced adenomas were defined as adenomas < 10 mm, without features of HGD or villous histology. Controls were defined as those without polyps at the current colonoscopy and without a history of colorectal polyps. Data collection included: anthropometrics measured according to a standardized protocol, fasting blood tests performed at the same lab, medical history recorded by a structured interview and dietary intake evaluated by a 116-item food frequency questionnaire. Adherence to the MD components was evaluated according to intake above/below the sample median, for potentially beneficial/detrimental components respectively, as accepted. RESULTS: We recruited 206 cases with advanced polyps, 192 cases with non-advanced adenoma and 385 controls. The number of adhered MD components was inversely associated with a diagnosis of advanced polyps in a dose-response manner (OR = 0.34, 95%CI: 0.17-0.65; OR = 0.22, 95%CI: 0.11-0.43; and OR = 0.18, 95%CI: 0.07-0.47 for 3-4, 5-7 and 8-10 components, respectively), but not with non-advanced adenomas (OR = 0.54, 95%CI: 0.25-1.13; OR = 0.48, 95%CI: 0.23-0.99; and OR = 0.43, 95%CI: 0.16-1.12 for 3-4, 5-7 and 8-10 components, respectively). Low intake of sugar-sweetened beverages and red meat, as well as high intake of fish, were inversely associated with advanced polyps (OR = 0.56, 95%CI: 0.36-0.87; OR = 0.63, 95%CI: 0.42-0.95; and OR = 0.66, 95%CI: 0.44-0.99, respectively), while only low intake of red meat was inversely associated with non-advanced adenomas (OR = 0.71, 95%CI: 0.49-0.97). CONCLUSION: A better adherence to the MD, specifically low intake of sugar-sweetened beverages and red meat as well as high intake of fish, is related to lower odds for advanced polyps.

Green tea extracts for the prevention of metachronous colorectal polyps among patients who underwent endoscopic removal of colorectal adenomas: A randomized clinical trial.

OBJECTIVES: To determine the preventive effect of green tea extract (GTE) supplements on metachronous colorectal adenoma and cancer in the Korean population. MATERIALS AND METHODS: One hundred seventy-six subjects (88 per each group) who had undergone complete removal of colorectal adenomas by endoscopic polypectomy were enrolled. They were randomized into 2 groups: supplementation group (0.9 g GTE per day for 12 months) or control group without GTE supplementation. The 72-h recall method was used to collect data on food items consumed by participants at baseline and the 1-year follow-up during the past 48 h. Follow-up colonoscopy was conducted 12 months later in 143 patients (71 in control group and 72 in the GTE group). RESULTS: Of the 143 patients completed in the study, the incidences of metachronous adenomas at the end-point colonoscopy were 42.3% (30 of 71) in control group and 23.6% (17 of 72) in GTE group (relative risk [RR], 0.56; 95% confidence interval [CI], 0.34-0.92). The number of relapsed adenoma was also decreased in the GTE group than in the control group (0.7 ± 1.1 vs. 0.3 ± 0.6, p = 0.010). However, there were no significant differences between the 2 groups in terms of body mass index, dietary intakes, serum lipid profiles, fasting serum glucose, and serum C-reactive protein levels (all p > 0.05). CONCLUSION: This study of GTE supplement suggests a favorable outcome for the chemoprevention of metachronous colorectal adenomas in Korean patients (ClinicalTrials.gov number, NCT02321969).

Chemopreventive effect of Myricetin, a natural occurring compound, on colonic chronic inflammation and inflammation-driven tumorigenesis in mice.

Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps. Histopathologic analysis showed that Myricetin could attenuate the degree of colonic inflammation and colorectal tumorigenesis. Further analysis showed that Myricetin strongly reduced the levels of inflammatory factors TNF-α, IL-1ß, IL-6, NF-κB, p-NF-κB, cyclooxygenase-2 (COX-2), PCNA and Cyclin D1 in the colonic tissues as analyzed by the assays of immunohistochemical staining, Western blotting and Q-RT-PCR. Our results demonstrated that Myricetin possesses the biological activities of chemoprevention colonic chronic inflammation and inflammation-driven tumorigenesis. We suggest that Myricetin could be developed as a promising chemopreventive drug for reducing the risk of colorectal cancer.

Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer.

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 µl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFß, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.

POTENTIAL PREVENTIVE EFFECT OF LACTOBACILLUS ACIDOPHILUS AND LACTOBACILLUS PLANTARUM IN PATIENTS WITH POLYPS OR COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)].

A Study Comparing Colorectal Cancer Screening Techniques.

Colorectal cancer is in the top 3 of both diagnosed cancers and deaths related to cancer in the United States. Despite this, Americans are continuing to forgo colorectal cancer screening as part of their preventive health maintenance. Screening helps identify precancerous and early cancerous lesions so they can be easily treated and cured. The purpose of this study was to compare the rates of detection of adenomatous (precursors to colorectal cancer) polyps and colorectal cancer in 2 groups of asymptomatic patients: one group undergoing standard colonoscopy and the other group undergoing standard colonoscopy in conjunction with fecal occult blood testing. A pilot study was performed using a total of 63 patients who were randomly allocated into 2 groups: those receiving standard colonoscopy as the control group and those receiving standard colonoscopy in conjunction with fecal occult blood testing as the intervention group. Research participants also completed demographic information as well as a survey evaluating their perceptions regarding colorectal cancer screening. This survey was adopted from a previous study that evaluates colorectal cancer disease awareness and patients' perceptions following a Health Belief Model. The results show that despite a detection rate of 41% of adenomatous polyps in the intervention group, there were no positive fecal occult blood testing specimens. The Health Belief Model survey revealed that most participants were appropriately aware of the seriousness and treatability of colorectal cancer. They also agreed that colorectal cancer screening guidelines were important and beneficial to follow.