A Few Spanish Pearls for the American Journal of Gastroenterology

In the Red Section of this issue of the American Journal of Gastroenterology , well-known specialists in their respective fi elds present highlights from gastroenterology research in Spain. Th ese reports illustrate how well-organized network collaborations could impact the scientific literature worldwide, as these collaborations are positioned at the frontier of knowledge and could reveal innovative approaches to the diagnosis and treatment of patients with digestive diseases. These achievements are especially notable, given that they occurred during a serious worldwide economic crisis that affected research in many countries, especially those that do not generally prioritize science. Most of the successes presented here were obtained under the umbrella of two national organizations. One is the CIBERehd, an acronym of the Spanish name “Centro de Investigation Biomédica en Red para Enfermedades Hepáticas y Digestivas” or “Biomedical Research Networking Center Consortium in Hepatic and Digestive Diseases” in English. The CIBERehd ( http://www.ciberehd.org ) is part of a larger entity known as “CIBER”, which has additional areas of interest focused on a variety of human diseases. The CIBER was initiated and organized by the National Institute of Health Carlos III ( http://www.eng.isciii.es ), in charge of coordinating Spanish biomedical research. The CIBERehd is a “virtual” center, combining the efforts of the best research groups in gastroenterology and hepatology across the country, and it funds, awards, and prioritizes collaborative research among the groups..

Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits

Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients

Colorectal cancer population screening programs worldwide in 2016: An update

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The incidence and mortality show wide geographical variations. Screening is recommended to reduce both incidence and mortality. However, there are significant differences among studies in implementation strategies and detection. This review aimed to present the results and strategies of different screening programs worldwide. We reviewed the literature on national and international screening programs published in PubMed, on web pages, and in clinical guidelines. CRC Screening programs are currently underway in most European countries, Canada, specific regions in North and South America, Asia, and Oceania. The most extensive screening strategies were based on fecal occult blood testing, and more recently, the fecal immunochemical test (FIT). Participation in screening has varied greatly among different programs. The Netherlands showed the highest participation rate (68.2%) and some areas of Canada showed the lowest (16%). Participation rates were highest among women and in programs that used the FIT test. Men exhibited the greatest number of positive results. The FIT test has been the most widely used screening program worldwide. The advent of this test has increased participation rates and the detection of positive results

Omega-3 Polyunsaturated Fatty Acids and Their Bioactive Metabolites in Gastrointestinal Malignancies Related to Unresolved Inflammation. A Review

Chronic inflammation takes part in the pathogenesis of some malignancies of the gastrointestinal tract including colorectal (CRC), gastric, and esophageal cancers. The use of omega 3 polyunsaturated fatty acid (omega 3-PUFA) supplements for chemoprevention or adjuvant therapy of gastrointestinal cancers is being investigated in recent years. Most evidence has been reported in CRC, although their protective role has also been reported for Helicobacter pylori-induced gastric cancer or Barrett''s esophagus-derived adenocarcinoma. Studies based on omega 3-PUFA supplementation in animal models of familial adenomatous polyposis (FAP) and CRC revealed positive effects on cancer prevention, reducing the number and size of tumors, down-regulating arachidonic acid-derived eicosanoids, upregulating anti-oxidant enzymes, and reducing lipid peroxidation, whereas contradictory results have been found in induced colitis and colitis-associated cancer. Beneficial effects have also been found in FAP and ulcerative colitis patients. Of special interest is their positive effect as adjuvants on radio- and chemo-sensitivity, specificity, and prevention of treatment complications. Some controversial results obtained in CRC might be justified by different dietary sources, extraction and preparation procedures of omega 3-PUFAs, difficulties on filling out food questionnaires, daily dose and type of PUFAs, adenoma subtype, location of CRC, sex differences, and genetic factors. Studies using animal models of inflammatory bowel disease have confirmed that exogenous administration of active metabolites derived from PUFAs called pro-resolving mediators like lipoxin A4, arachidonic acid-derived, resolvins derived from eicosapentaenoic (EPA), docosahexaenoic (DHA), and docosapentaenoic (DPA) acids as well as maresin 1 and protectins DHA- and DPA-derived improve disease and inflammatory outcomes without causing immunosuppression or other side effects

Gastrointestinal Safety of Aspirin for a High-Dose, Multiple-Day Treatment Regimen: A Meta-Analysis of Three Randomized Controlled Trials

Background and Aim: Aspirin is a commonly used over-the-counter (OTC) agent for the symptomatic treatment of acute pain, fever, or the common cold, but data regarding safety in this context are limited. In order to characterize the safety of aspirin beyond single-dose or long-term use data, we conducted a meta-analysis of multiple-dose, multiple-day studies of OTC aspirin at a label-approved dosage. Methods: We conducted a meta-analysis of individual patient data from three Bayer-sponsored studies. The meta-analysis was performed in 2015; the individual studies were conducted between 2008 and 2012 and were of a randomized, parallel-group, placebo-controlled design. Patients received a minimum dosage of aspirin of 2000 mg/day over at least 3 days. The endpoints were patient-reported adverse events (AEs) with an emphasis on the system organ class gastrointestinal system. Event incidences were estimated and an analysis of the odds ratios (ORs) and risk differences (RDs) of aspirin versus placebo were performed. Results: Of the 819 patients included, 433 were treated with aspirin and 386 were treated with placebo. The majority of patients (85.7 %) received a median dose of aspirin of 3000 mg/day for 3 days. The incidence of the overall AEs was low and rates were comparable between the aspirin (10.9 %) and placebo (12.4 %) groups [OR: 0.86 (95 % confidence interval [CI] 0.56, 1.34); RD: -1.49 (95 % CI -6.01, 3.03)]. Gastrointestinal AEs were more common in subjects treated with aspirin (7.4 %) than with placebo (5.4 %), and although this difference did not reach statistical significance, a trend towards increased risk was observed with aspirin use [OR: 1.41 (95 % CI 0.78, 2.54); RD: 2.00 (95 % CI -1.35, 5.35)]. Nausea, upper abdominal pain, dyspepsia, and diarrhea were the most frequently reported gastrointestinal AEs. There were no reports of serious gastrointestinal complications such as bleeding, perforation, or ulceration.: Conclusions: The multiple-dose regimen of aspirin used for several days according to the OTC label is well-tolerated by otherwise healthy non-elderly subjects for short-term and symptomatic treatment of pain, fever, and the common cold. There were no reports of serious gastrointestinal complications in either of the groups

A review of the gastrointestinal safety data—a gastroenterologist’s perspective

Although NSAIDs have a well-established place for certain indications in the management of OA and RA, they are associated with significant gastrointestinal (GI) toxicity. The risk of NSAID-related upper GI events, such as dyspepsia or peptic ulcer and complications such as perforation or bleeding, is well characterized. Non-selective NSAIDs increase the risk of peptic ulcer disease ∼5-fold, and that of upper GI bleeding 4-fold, whereas selective cyclo-oxygenase-2 (COX) inhibitors are associated with a significantly lower GI toxicity than non-selective agents. There is evidence that, while the incidence of NSAID-related upper GI complications has decreased in recent years, that of lower GI complications is increasing. Observational studies and analyses from studies, primarily designed to investigate upper GI events, suggest that lower GI complications are relatively common in NSAID users and that COX-2 selective inhibitors are associated with a lower risk of these events. Such events have been poorly characterized, but are associated with significant mortality; indeed, they may have even more serious consequences than the better characterized upper GI events. There is thus a strong case for evaluating the impact of such complications in prospective outcome studies. To facilitate such studies a new endpoint, Clinically Significant Upper or Lower GI Events, has been introduced that captures both upper and lower GI events

Deconvolution analysis for classifying gastric adenocarcinoma patients based on differential scanning calorimetry serum thermograms

Recently, differential scanning calorimetry (DSC) has been acknowledged as a novel tool for diagnosing and monitoring several diseases. This highly sensitive technique has been traditionally used to study thermally induced protein folding/unfolding transitions. In previous research papers, DSC profiles from blood samples of patients were analyzed and they exhibited marked differences in the thermal denaturation profile. Thus, we investigated the use of this novel technology in blood serum samples from 25 healthy subjects and 30 patients with gastric adenocarcinoma (GAC) at different stages of tumor development with a new multiparametric approach. The analysis of the calorimetric profiles of blood serum from GAC patients allowed us to discriminate three stages of cancer development (I to III) from those of healthy individuals. After a multiparametric analysis, a classification of blood serum DSC parameters from patients with GAC is proposed. Certain parameters exhibited significant differences (P < 0.05) and allowed the discrimination of healthy subjects/patients from patients at different tumor stages. The results of this work validate DSC as a novel technique for GAC patient classification and staging, and offer new graphical tools and value ranges for the acquired parameters in order to discriminate healthy from diseased subjects with increased disease burden

Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - Gastrointestinal adverse effects: A meta-analysis of randomized clinical trials

Background and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported

Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199, 049 new users of low-dose aspirin (75-300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case-control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54-0.88) for >1 month PPI use and 2.65 (1.62-4.3) for 1 month PPI use and 1.12 (0.73-1.71) for 1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk