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Among 1676 persons with H. pylori infection who had family members with gastric cancer, the incidence of gastric cancer over a median follow-up of 9.2 years was significantly lower among those who received eradication treatment for H. pylori infection than among those who received placebo.

Among 88,902 participants followed over a period of 22 years in the Nurses' Health Study and the Health Professionals Follow-up Study, colon cancer mortality was reduced after screening sigmoidoscopy (hazard ratio, 0.59) and screening colonoscopy (hazard ratio, 0.32). Randomized, controlled trials have shown that screening with flexible sigmoidoscopy reduces the incidence of colorectal cancer and associated mortality, albeit with diminished effectiveness for cancers of the proximal colon. 1 – 3 Although comparable data from randomized, controlled trials of screening colonoscopy are not yet available, 4 colonoscopy is also widely endorsed by expert bodies for population-based screening, largely on the basis of case–control studies that show associations with reduced colorectal-cancer incidence and mortality. 5 – 9 However, as with flexible sigmoidoscopy, there is uncertainty about the effectiveness of colonoscopy in reducing the incidence of and mortality associated with proximal colon cancer 10 – 19 and about . . .

The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. 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). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). 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. Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Here, we show that autophagy is activated in the intestinal epithelium in murine and human colorectal cancer and that the conditional inactivation of Atg7 in intestinal epithelial cells inhibits the formation of pre-cancerous lesions in Apc +/− mice by enhancing anti-tumour responses. The antibody-mediated depletion of CD8 + T cells showed that these cells are essential for the anti-tumoral responses mediated by the inhibition of autophagy. We show that Atg7 deficiency leads to intestinal dysbiosis and that the microbiota is required for anticancer responses. In addition, Atg7 deficiency resulted in a stress response accompanied by metabolic defects, AMPK activation and p53-mediated cell-cycle arrest in tumour cells but not in normal tissue. This study reveals that the inhibition of autophagy within the epithelium may prevent the development and progression of colorectal cancer in genetically predisposed patients. Romagnolo and colleagues report that Atg7 deficiency has a tumour-suppressive role in the intestinal epithelium, by inducing a microbiome-influenced immune response and inhibiting tumour growth through p53- and AMPK-related mechanisms.

On the basis of long-term follow-up data from the National Polyp Study, the authors estimate that mortality from colorectal cancer was about 50% lower among patients who had adenomatous polyps removed than in the general population. It has been a long-standing belief that screening for colorectal cancer can affect mortality from the disease in two ways: by detecting cancers at an early, curable stage and by detecting and removing adenomas. 1 Detection of early-stage colorectal cancer has been shown to be associated with a reduction in mortality from colorectal cancer in screening trials. 2 – 4 However, an adenomatous polyp is a much more common neoplastic finding on endoscopic screening. We previously reported that colonoscopic polypectomy in the National Polyp Study (NPS) cohort reduced the incidence of colorectal cancer. 5 An important question is whether the cancers prevented by colonoscopic . . .

There are striking inequities in calcium intake between rich and poor populations. Appropriate calcium intake has shown many health benefits, such as reduction of hypertensive disorders of pregnancy, lower blood pressure particularly among young people, prevention of osteoporosis and colorectal adenomas, lower cholesterol values, and lower blood pressure in the progeny of mothers taking sufficient calcium during pregnancy. Studies have refuted some calcium supplementation side effects like damage to the iron status, formation of renal stones and myocardial infarction in older people. Attention should be given to bone resorption in post-partum women after calcium supplementation withdrawal. Mechanisms linking low calcium intake and blood pressure are mediated by parathyroid hormone raise that increases intracellular calcium in vascular smooth muscle cells leading to vasoconstriction. At the population level, an increase of around 400–500 mg/day could reduce the differences in calcium intake between high- and middle-low-income countries. The fortification of food and water seems a possible strategy to reach this goal.

In this placebo-controlled trial involving patients with recently diagnosed adenomas, daily supplementation with vitamin D 3 (1000 IU), calcium (1200 mg), or both did not reduce the risk of recurrent colorectal adenomas over 3 to 5 years. Vitamin D, an essential nutrient that is important for bone mineralization and calcium homeostasis, 1 also has effects beyond bone and calcium. Many studies have shown it to be antineoplastic, particularly in the colorectum. In in vitro studies, vitamin D and its analogues have been shown to inhibit proliferation, induce differentiation, inhibit angiogenesis, and promote apoptosis in epithelial tissues. 2 , 3 High vitamin D intake inhibits experimental carcinogenesis, 2 , 3 even in animals that are vitamin D–replete. 4 Observational studies of vitamin D intake 5 – 7 and serum levels of 25-hydroxyvitamin D 8 – 10 have shown inverse associations between these measures and the risk of colorectal . . .

It recently has been recognized that men develop colonic adenomas and carcinomas at an earlier age and at a higher rate than women. In the Apc ᴾⁱʳᶜ/⁺ (Pirc) rat model of early colonic cancer, this sex susceptibility was recapitulated, with male Pirc rats developing twice as many adenomas as females. Analysis of large datasets revealed that the Apc ᴹⁱⁿ/⁺ mouse also shows enhanced male susceptibility to adenomagenesis, but only in the colon. In addition, WT mice treated with injections of the carcinogen azoxymethane (AOM) showed increased numbers of colonic adenomas in males. The mechanism underlying these observations was investigated by manipulation of hormonal status. The preponderance of colonic adenomas in the Pirc rat model allowed a statistically significant investigation in vivo of the mechanism of sex hormone action on the development of colonic adenomas. Females depleted of endogenous hormones by ovariectomy did not exhibit a change in prevalence of adenomas, nor was any effect observed with replacement of one or a combination of female hormones. In contrast, depletion of male hormones by orchidectomy (castration) markedly protected the Pirc rat from adenoma development, whereas supplementation with testosterone reversed that effect. These observations were recapitulated in the AOM mouse model. Androgen receptor was undetectable in the colon or adenomas, making it likely that testosterone acts indirectly on the tumor lineage. Our findings suggest that indirect tumor-promoting effects of testosterone likely explain the disparity between the sexes in the development of colonic adenomas. Significance The age-adjusted incidence of colonic adenomas and colorectal cancer is higher in men than in women. In a careful analysis of two established animal models, we found that castration reduced, and testosterone supplementation restored, the number of adenomas in the male rat and mouse colon, whereas ovariectomy and replacement of female hormones had no measureable effect on colonic adenomagenesis. In Min mice, in which most of the tumors arise in the small intestine, this testosterone-dependent sexual dimorphism in mice was specific to the colon. Our results support a paradigm shift: Testosterone promotes early adenomagenesis through an indirect mechanism, explaining the enhanced susceptibility of males to colonic adenomagenesis in the human, rat, and mouse.

BackgroundThree large randomised trials have shown that screening for colorectal cancer (CRC) using the faecal occult blood test (FOBt) can reduce the mortality from this disease. The largest of these trials, conducted in Nottingham since 1981, randomised 152 850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult (FOB) test kit or to a control arm. In 2006, the National Bowel Cancer Screening Programme was launched in England using the FOBt, with the expectation that it will reduce CRC mortality.AimsTo compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up.MethodsThe 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics).ResultsAt a median follow-up of 19.5 years there was a 13% reduction in CRC mortality (95% CI 3% to 22%) in the intervention arm despite an uptake at first invitation of approximately 57%. The CRC mortality reduction in those accepting the first screening test, adjusted for the rate of non-compliers, was 18%. There was no significant difference in mortality from causes other than CRC between the intervention and control arms. Despite removing 615 adenomas >10 mm in size from the intervention arm, there was no significant difference in CRC incidence between the two arms.ConclusionsAlthough the reduction in CRC mortality was sustained, further follow-up of the screened population has not shown a significant reduction in the CRC incidence. Moreover, despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour.