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Aldo Lorenzetti M.D, Internal Medicine & Hepatology, Milano - SIMEDET Delegate
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#Colorectal Cancer #Incidence Patterns in the United States, 1974–2013

https://academic.oup.com/jnci/article/doi/10.1093/jnci/djw322/3053481/Colorectal-Cancer-Incidence-Patterns-in-the-United

Age-specific CRC risk has escalated back to the level of those born circa 1890 for contemporary birth cohorts, underscoring the need for increased awareness among clinicians and the general public, as well as etiologic research to elucidate causes for the trend. Further, as nearly one-third of rectal cancer patients are younger than age 55 years, screening initiation before age 50 years should be considered.
Origins of #lymphatic and distant metastases in human #colorectal #cancer http://science.sciencemag.org/content/357/6346/55

The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes

We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin.
Re-analysis of All-Cause #Mortality in the U.S. Preventive Services Task Force 2016 Evidence Report on #Colorectal Cancer Screening
http://annals.org/aim/article/2650649/re-analysis-all-cause-mortality-u-s-preventive-services-task

Background: The 2016 U.S. Preventive Services Task Force (USPSTF) evidence report on colorectal cancer screening concluded that no colorectal cancer screening methods reduce all-cause mortality. This conclusion was partially based on a meta-analysis of 4 randomized trials that compared flexible sigmoidoscopy screening with no screening. The meta-analysis aggregated results from the 2 age cohorts of 1 of the trials—the NORCCAP (Norwegian Colorectal Cancer Prevention) study—as if these cohorts were a single trial (1). Aggregation of outcomes that have markedly different event rates, screening–control ratios, or both can create a Simpson paradox, a phenomenon where a finding exists in individual data groups that is absent or opposite when the groups are combined
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#Colorectal cancer #screening for average‐risk adults: 2018 guideline update from the American Cancer Society

https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21457


The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high‐sensitivity stool‐based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation.

The ACS recommends (qualified recommendations) that: 1) average‐risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high‐sensitivity, guaiac‐based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years
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Influence of Varying Quantitative #Fecal Immunochemical Test Positivity Thresholds on #Colorectal Cancer Detection: A Community-Based Cohort Study

http://annals.org/aim/article-abstract/2702473/influence-varying-quantitative-fecal-immunochemical-test-positivity-thresholds-colorectal-cancer

Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011)

Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources
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Association of #Obesity With Risk of Early-Onset #Colorectal Cancer Among Women

https://jamanetwork.com/journals/jamaoncology/article-abstract/2705608

Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend).

Conclusions and Relevance Obesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.
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Time to Colonoscopy and Risk of #Colorectal Cancer in Patients With Positive Results From Fecal #Immunochemical Tests

https://www.cghjournal.org/article/S1542-3565(18)31207-2/fulltext

In our cohort, 2003 patients received a diagnosis of any CRC and 445 patients were found to have advanced-stage disease. Compared with colonoscopy within 1–3 months (cases per 1000 patients: 50 for any CRC and 11 for advanced-stage disease), risks were significantly higher when colonoscopy was delayed by more than 6 months for any CRC (aOR, 1.31; 95% CI, 1.04–1.64; 68 cases per 1000 patients) and advanced-stage disease (aOR, 2.09; 95% CI, 1.43–3.06; 24 cases per 1000 patients). The risks continuously increased when colonoscopy was delayed by more than 12 months for any CRC (aOR, 2.17; 95% CI, 1.44–3.26; 98 cases per 1000 patients) and advanced-stage disease (aOR, 2.84; 95% CI, 1.43–5.64; 31 cases per 1000 patients). There were no significant differences for colonoscopy follow up at 3–6 months for risk of any CRC (aOR, 0.98; 95% CI, 0.86–1.12; 49 cases per 1000 patients) or advanced-stage disease (aOR, 0.95; 95% CI, 0.72–1.25; 10 cases per 1000 patients).

Conclusion
In an analysis of data from the Taiwanese Nationwide Screening Program, we found that among patients with positive results from a FIT, risks of CRC and advanced-stage disease increase with time. These findings indicate the importance of timely colonoscopy after a positive result from a FIT.
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#Eicosapentaenoic acid and #aspirin, alone and in combination, for the prevention of #colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31775-6/fulltext

The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio RR 0·98, 95% CI 0·87 to 1·12; risk difference −0·9%, −8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference −0·6%, −8·5 to 7·2; p=0·88)...

Interpretation
Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.
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Sex differences in faecal occult #blood test screening for #colorectal cancer

https://onlinelibrary.wiley.com/doi/10.1002/bjs.11011

CRC was less common in women than in men (0·34 versus 0·50 per cent; risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·91) and women were less often asymptomatic (16·7 versus 22·0 per cent; RR 0·76, 0·61 to 0·93). Women more often had right‐sided tumours (32·0 versus 21·3 per cent; RR 1·51, 1·26 to 1·80). Among men with left‐sided tumours, those in the screening arm had lower N (RR 1·23, 1·02 to 1·48) and M (RR 1·57, 1·14 to 2·17) categories, as well as a higher overall survival rate than those in the control arm. Furthermore among men with left‐sided tumours, non‐radical resections (26·2 versus 15·7 per cent; RR 1·67, 1·22 to 2·30) and postoperative chemotherapy sessions (61·6 versus 48·2 per cent; RR 1·28, 1·10 to 1·48) were more frequent in the control arm. Similar benefits of screening were not detected in men with right‐sided tumours or in women.

Conclusion

Biennial FOBT screening seems to be effective in terms of improving several different outcomes in men, but not in women. Differences in incidence, symptoms and tumour location may explain the differences in screening efficacy between sexes.
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Association of #Chemerin Plasma Concentration With Risk of #Colorectal Cancer

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2728622

Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions.

In multivariable-adjusted Cox proportional hazards regression models taking into account established CRC risk factors, higher chemerin concentrations were associated with a greater risk of CRC, with a hazard ratio (HR) of 1.81 (95% CI, 1.08-3.05; P for trend = .007) for the highest chemerin quartile vs the lowest. Analyses by cancer subsite indicated a stronger association with colon cancer (HR, 2.27; 95% CI, 1.18-4.34 for the highest quartile vs the lowest; P for trend = .005) compared with rectal cancer (HR, 1.27; 95% CI, 0.57-2.85; P for trend = .35). The association was particularly strong for proximal colon cancer (HR, 3.97; 95% CI, 1.51-10.50; P for trend = .001).

Conclusions and Relevance

This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.
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Oral #antibiotic use and risk of #colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study

https://gut.bmj.com/content/early/2019/07/11/gutjnl-2019-318593

..Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic–cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).

Conclusion Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.
#Colorectal Cancer Risk Following #Bariatric Surgery in a Nationwide Study of French Individuals With Obesity
https://2medical.news/2020/03/18/colorectal-cancer-risk-following-bariatric-surgery-in-a-nationwide-study-of-french-individuals-with-obesity/

..The mean (SD) follow-up was 6.2 (2.1) years for patients who underwent adjustable gastric banding, 5.5 (2.1) years for patients who underwent sleeve gastrectomy, and 5.7 (2.2) years for patients who underwent gastric bypass. In total, 13 052 incident colorectal cancers (1.2%) and 63 649 colorectal benign polyps were diagnosed. The rate of colorectal cancer was 0.6% in the bariatric surgery cohort and 1.3% in the cohort …
#ACE (Angiotensin-Converting Enzyme) Inhibitors/Angiotensin Receptor Blockers Are Associated With Lower #Colorectal Cancer Risk
https://2medical.news/2020/07/11/ace-angiotensin-converting-enzyme-inhibitors-angiotensin-receptor-blockers-are-associated-with-lower-colorectal-cancer-risk/

Whether ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers modify colorectal cancer risk remains controversial. We aimed to determine association between their use and colorectal cancer risk after a negative baseline colonoscopy. This is a territory-wide retrospective cohort study recruiting patients aged ≥40 who had undergone colonoscopy between 2005 and 2013. Exclusion criteria included colorectal cancer detected <6 months of index colonoscopy, prior colorectal cancer, …
Association of #Coffee Intake With Survival in Patients With Advanced or Metastatic #Colorectal Cancer
https://2medical.news/2020/09/21/association-of-coffee-intake-with-survival-in-patients-with-advanced-or-metastatic-colorectal-cancer/

Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown.. ..Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 …
ACG Clinical Guidelines: #Colorectal #Cancer Screening 2021
https://2medical.news/2021/03/12/acg-clinical-guidelines-colorectal-cancer-screening-2021/

1. We recommend CRC screening in average-risk individuals between ages 50 and 75 years to reduce incidence of advanced adenoma, CRC, and mortality from CRC. Strong recommendation; moderate-quality evidence 2. We suggest CRC screening in average-risk individuals between ages 45 and 49 years to reduce incidence of advanced adenoma, CRC, and mortality from CRC. Conditional recommendation; very low-quality evidence 3. We suggest that a decision …