Angel Ferrandez

Inappropriate prevention of NSAID-induced gastrointestinal events among long-term users in the elderly.

Although use of NSAIDs and aspirin (acetylsalicylic acid) is well known to be associated with gastrointestinal (GI) complications and potential mortality, these medications continue to be widely prescribed in the elderly. Age is a significant risk factor for NSAID-induced GI events; indeed, patients >75 years of age carry the highest risk and are similar in this respect to patients with a history of peptic ulcer. Prevention of NSAID-induced gastropathy is indicated in patients at risk. It is accepted that patients >60 years of age taking NSAIDs should participate in prevention strategies such as co-therapy with proton pump inhibitors (PPIs) or misoprostol, or use of cyclo-oxygenase (COX)-2 selective NSAIDs (also called coxibs). Although up to 33% of subjects with no risk factors who receive NSAIDs over-utilise GI preventive therapies, under-utilisation of gastroprotective therapy is more prevalent among those with risk factors, of which the most frequent is age. At least half of those at risk do not receive appropriate preventive therapy, either because they do not receive co-therapy with PPIs or misoprostol or are not treated with COX-2 selective NSAIDs, or because they receive co-therapy with antacids or histamine H2 receptor antagonists, which are not effective. Adherence to the prescribed preventive therapy is an additional problem for those who are prescribed a PPI or misoprostol. Over 30% of patients are non-adherent and the lowest rate of non-adherence is associated with the first NSAID prescription, which increases the risk of ulcer bleeding compared with those who are fully adherent. Predictors of nonadherence include long-term use of NSAIDs and a high average daily dose of NSAIDs. Predictors of adherence include a history of upper gastrointestinal events, anticoagulant use, rheumatological disease and use of low-dose salicylates, among others. Another important aspect is self-medication; this is common in the elderly, who also have several risk factors for GI complications, and may be a factor in over one-third of all NSAID-related complications. In summary, aging is a key risk factor for GI complications in patients taking NSAIDs. Appropriate prevention strategies should be used in the elderly and those at risk; special attention should be paid to compliance and self-medication.

COX-2 and colorectal cancer.

Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.

CagA-positive Helicobacter pylori infection is not associated with decreased risk of Barrett's esophagus in a population with high H. pylori infection rate

Background & aimThe role that H. pylori infection plays in the development of and Barretts esophagus (BE) is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE.MethodsWe studied 104 consecutive patients, residents in an area with a high prevalence of H. pylori infection, with BE and 213 sex- and age-matched controls. H. pylori infection and CagA antibody status were determined by western blot serology.ResultsH. pylori prevalence was higher in patients with BE than in controls (87.5% vs. 74.6%; OR. 2.3; 95% CI: 1.23–4.59). Increasing age was associated with a higher prevalence of H. pylori (p < 0.05). The prevalence of CagA+ H. pylori serology was similar in patients with BE and controls (64.4% vs. 54.5%; NS). Type I H. pylori infection (CagA+ and VacA+) was similar in patients with BE and controls (44.2% vs. 41.3%; NS). Logistic regression analysis identified alcohol (O.R. 7.09; 95% CI 2.23–22.51), and H. pylori infection (OR: 2.41; 95%CI: 1.20–4.84) but not CagA+ serology as independent factors.ConclusionNeither H. pylori infection nor H. pylori infection by CagA+ strains reduce the risk of BE in a population with high prevalence of H. pylori infection.

Aspirin and the prevention of colorectal cancer

A large body of evidence from basic science, epidemiologic observations and population-based studies demonstrates that aspirin, as well as other non-steroidal anti-inflammatory drugs, has a chemopreventive effect on several cancer types and, more specifically, in CRC. This protective effect includes prevention of adenoma recurrence and reduction of CRC incidence and mortality. Although the protective effect appears to depend on the dose and the drug, the most important factor is the duration of exposure. However, the lowest effective dose, treatment duration, specific target populations, and effects on survival have not been defined yet. More important, data on the risk-benefit profile for cancer prevention are insufficient and, accordingly, no definitive recommendation can be made at present. In this article, besides reviewing current knowledge of the mechanisms involved in aspirin-based CRC chemoprevention, we will be focused on randomized controlled studies assessing its efficacy in high-, moderate- and average-risk populations.

NSAIDs and the colon.

Purpose of review To better understand the effects of NSAIDs on the colon. Recent findings An epidemiological study has confirmed that NSAIDs increase the risk of hospitalizations for lower gastrointestinal complications, though the estimated rate of hospitalization was lower than that for upper gastrointestinal complications. Proton-pump inhibitors were associated with reduction in hospitalizations for upper but not lower gastrointestinal complications. Current research on cyclooxygenase (COX) inhibition in patient and animal models suggests that COX-1 and COX-2 may have different roles in the exacerbation of inflammatory bowel disease. Epidemiological research on the chemoprevention of colorectal cancer with aspirin suggests that the positive effect of risk reduction is only observed after long-term treatment. The search for targets of chemopreventive drugs is ongoing. COX-2 inhibition still seems preferred option, as the effects observed with aspirin (the only chemopreventive agent with some apparent future) are more profound only in tumors and cells expressing COX-2. Other molecules such as nitric oxide NSAIDs, especially nitric oxide aspirin, are under intensive experimental research. Summary NSAID use increases the risk of hospitalizations due to complications in the lower gastrointestinal tract. By inhibiting COX-2 or other tumorigenic targets, NSAIDs, especially aspirin or new aspirin derivates, may prevent colon cancer in selected populations.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity

In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase‐generated cytokeratin‐18 (CK‐18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase‐generated CK‐18 fragments in patients with severe obesity.

Colonic Adenoma Risk in Familial Colorectal Cancer – a Study of Six Extended Kindreds

OBJECTIVES:Most colorectal cancers (CRCs) arise from adenomatous polyps, but the effects of CRC family history on adenoma risk are not well known. This issue is clinically relevant since several medical societies currently recommend earlier and more rigorous colorectal screening for individuals with a strong family history of CRC.METHODS:Colonoscopies were performed in 236 first-, second-, and third-degree relatives of 40 index CRC cases from six large kindreds selected from a large population database. The kindreds were selected for significantly greater risk of CRCs compared with the overall population. Known hereditary colon cancer syndromes were clinically and genetically excluded.RESULTS:Thirty-seven percent of relatives were found to have adenomas on colonoscopy. The average age of diagnosis for colon cancer was 63 yr and advanced adenomas 56 yr. Independent predictors of adenomatous polyps in the relatives were advancing age (P < 0.0001), male gender (P < 0.001), and greater degree of relation to CRC cases (P < 0.01). There was no significant predilection of colorectal tumors for the right or left colon. A higher degree of relationship to CRC cases was a significant predictor of having simple and advanced adenomas, but not hyperplastic polyps after adjustment for age and gender.CONCLUSIONS:These data support the current recommendations for colonoscopy starting before the age of 50 yr in individuals with a strong family history of CRC.

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.

Incomplete type of intestinal metaplasia has the highest risk to progress to gastric cancer: results of the Spanish follow‐up multicenter study

In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence.

Selective COX-2 inhibition is associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis.

Objective: To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits. Methods: Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h). Results: Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis. Conclusions: COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.