Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in the pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min); nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites.

Summary: Background: Patients with gastrointestinal bleeding during anticoagulant and/or antiplatelet therapy represent a clinical challenge.Aim: To determine the risk/rates of rebleeding, vascular events and death in patients treated with antiplatelet or anticoagulant agents who developed major gastrointestinal bleedingMethods: This was an observational cohort study of patients who developed gastrointestinal bleeding while on antiplatelet and/or anticoagulant therapy. Drug use information was collected prospectively during bleeding events. Cox proportional hazards models were used to evaluate rebleeding, vascular events and death.Results: Among 871 patients (mean age 78.9 ± 8.6 years), 38.9% used an anticoagulant, 52.5% used an antiplatelet and 8.6% used both; 93.1% interrupted treatment after gastrointestinal bleeding and 80.5% restarted therapy within 7.6 ± 36.4 days; 38.7% had upper gastrointestinal bleeds, 46.7% lower gastrointestinal bleeds and 14.6% gastrointestinal bleeds of unknown origin. Median follow‐up was 24.9 months (IQR: 7.0‐38.0). Resumption of both therapies was associated with a higher risk of rebleeding, lower risk of ischaemic events or death and a similar risk for upper and lower gastrointestinal events. Resumption of therapy ≤ 7 days after bleeding showed a similar pattern with no differences in death. Rebleeding rates were higher in anticoagulant vs antiplatelet patients (138.0 vs 99.0 events per 1000 patient‐years), and the bleeding location was identical in 61.8% of cases.Conclusions: Resumption of anticoagulant or antiplatelet therapy after a gastrointestinal bleeding event was associated with a lower risk of vascular events and death and a higher rebleeding risk. The benefits of early reinstitution of anticoagulant/antiplatelet therapy outweigh the gastrointestinal‐related risks.

Background: Faecal occult blood test (FOBT) has demonstrated effectiveness in colorectal cancer (CRC) screening. Faecal calprotectin (FC) has proven efficient for evaluating activity in inflammatory bowel disease (IBD), but its value in CRC detection is less established. Most symptomatic patients have benign pathologies, but still undergo colonoscopy in many settings. Aims: To evaluate the diagnostic accuracy and cost-effectiveness of the combination of FOBT plus FC in symptomatic patients. Methods: Patients who completed colonic investigations and returned stool samples, on which FOBT and FC were performed, were recruited prospectively. CRC, advanced adenoma, IBD and angiodysplasia were considered as relevant pathologies. Results: A total of 404 patients were included, of whom 87 (21.5%) had relevant pathologies. Sensitivity and specificity were 50.6% and 69.6% for FOBT, 78.2% and 54.4% for FC. Negative predictive value (NPV) was 90.1% for FC and 86.9% for FOBT. NPV for the combination of FOBT and FC was 94.1%, with a sensitivity and specificity of 88.5% and 50.3%. The area under ROC (receiver operator curve) (AUC) was 0.741 for FOBT, 0.736 for FC and 0.816 for the combination. The total cost for visits and procedures was €233,016 (€577/patient). Using a combination of FOBT and FC as pre-endoscopic tool allows colonoscopies to be reduced by 39.4%, reducing total costs by 20.5%. Conclusion: The combination of FOBT and FC has a better diagnostic accuracy compared with each test alone. Performing both tests before colonoscopy is a less costly and more effective strategy, reducing unnecessary procedures and complications.

Background: The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. Objectives and methods: To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Results: Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32–5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. Conclusions: The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

Low dose aspirin (ASA), commonly defined as the cardiovascular (CV) dose of 75 to 325 mg daily, is one of the most widely prescribed drugs in the world and the cornerstone of therapy and prophylaxis for CV disease. However, the use of low dose ASA is well known to be associated with an increased risk of different upper and lower gastrointestinal (GI) complications, such as peptic ulceration and bleeding. In the recent past, clinical research was mainly focused on ASA-related injury of the upper GI tract. However, the introduction of new endoscopic techniques, such as capsule endoscopy and balloon-assisted endoscopy for the evaluation of small bowel lesions have resulted in an increasing interest among gastroenterologists about the side effects of ASA on the large and small bowel. Furthermore, it has been demonstrated that chronic use of low dose ASA results in a variety of lesions in the lower GI tract, including multiple petechiae, erosions, ulcers, diverticular bleeding and even circumferential ulcers with stricture. The ideal treatment for small bowel injury in low dose ASA users would be withdrawal of ASA, however, this withdrawal could increase the risk of CV/cerebrovascular morbidity and mortality in high percentage of patients. Therefore, several drugs have been evaluated to identify the best choice to prevent or treat ASA-induced small bowel injury with different results. Nevertheless, further specifically designed studies with more sample size are needed to determine the best treatment for low dose ASA related GI injury.