Ramiz Iqbal

Low Rate of Postpolypectomy Bleeding Among Patients Who Continue Thienopyridine Therapy During Colonoscopy

BACKGROUND & AIMS It is not clear whether the cardiovascular risk of discontinuing treatment with antiplatelet agents, specifically the thienopyridines, before elective colonoscopy outweighs the risks of postpolypectomy bleeding (PPB). We studied the rate of PPB in patients who continue thienopyridine therapy during colonoscopy. METHODS We performed a prospective study of 516 patients not taking warfarin who received polypectomies during elective colonoscopies; 219 were receiving thienopyridines, and 297 were not (controls). The occurrence of immediate PPB and delayed PPB was recorded. Delayed PPB was categorized as clinically important if it resulted in repeat colonoscopy, hospitalization, or blood transfusion. RESULTS Patients receiving thienopyridines were older and had significantly more comorbid diseases than controls; the mean number of polyps removed per patient was significantly higher (3.9 vs 2.9) in the thienopyridine group. Immediate PPB developed in 16 patients in the thienopyridine group (7.3%) and in 14 in the control group (4.7%, P = .25). Among patients who completed a 30-day follow-up analysis (96% of patients enrolled), clinically important, delayed bleeding occurred in 2.4% of patients receiving thienopyridines and in none of the controls (P = .01). All PPB events in both groups were resolved without surgery, angiography, or death. CONCLUSIONS Although a significantly higher percentage of patients who continue thienopyridine therapy during colonoscopy and polypectomy develop clinically important delayed PPB than patients who discontinue therapy, the rate of PPB events is low (2.4%), and all are resolved without sequelae. The risk for catastrophic cardiovascular risks among patients who discontinue thienopyridine therapy before elective colonoscopies could therefore exceed the risks of PPB. ClinicalTrials.gov, Number NCT01647568.

Clinical implications of histologic abnormalities in colonic biopsy specimens from patients with ulcerative colitis in clinical remission.

Background:For patients with ulcerative colitis (UC) who have colonoscopy while their disease is in clinical remission, the clinical implications of finding histologic abnormalities of colitis are not clear. Methods:We reviewed the medical records of patients with UC who had elective colonoscopy at our VA Medical Center while their UC was in clinical remission and who had at least 6 months of follow-up data available. The Mayo endoscopic subscore was used to assess endoscopic disease activity. Biopsies were evaluated for specific changes in the following general categories: acute inflammation, chronic inflammation, epithelial damage, and architectural distortion. Results:We identified 51 patients with UC who had a total of 84 colonoscopies (at least 1 year apart) while they were in clinical remission. Forty colonoscopies revealed no endoscopic activity (Mayo subscore 0) and 44 showed endoscopic activity (Mayo subscore 1, 2, or 3). Although flares were approximately twice as common in patients with endoscopic activity as in those with an endoscopically normal mucosa, the difference was not statistically significant. On histologic evaluation, in contrast, the presence of basal lymphoplasmacytosis, basally located lymphoid aggregates, erosions and/or ulcerations of the epithelium, or moderate to marked architectural distortion all were significant predictors of clinical flares by 6 and 12 months. Conclusions:For patients with UC who have colonoscopy while their disease is in clinical remission, colonic biopsy seems to provide important prognostic information beyond that provided by the endoscopic assessment of disease activity alone.

Case-control study of factors that trigger inflammatory bowel disease flares

AIM To explore the association between inflammatory bowel diseases (IBD) flares and potential triggers. METHODS Patients evaluated for an acute flare of IBD by a gastroenterologist at the Dallas VA Medical Center were invited to participate, as were a control group of patients with IBD in remission. Patients were systematically queried about nonsteroidal anti-inflammatory drug use, antibiotic use, stressful life events, cigarette smoking, medication adherence, infections, and travel in the preceding 3 mo. Disease activity scores were calculated for each patient at the time of enrollment and each patients chart was reviewed. Multivariate regression analysis was performed. RESULTS A total of 134 patients with IBD (63 with Crohns disease, 70 with ulcerative colitis, and 1 with indeterminate colitis) were enrolled; 66 patients had flares of their IBD and 68 were controls with IBD in remission (for Crohns patients, average Crohns disease activity index was 350 for flares vs 69 in the controls; for UC patients, Mayo score was 7.6 for flares vs 1 for controls in those with full Mayo available and 5.4p for flares vs 0.1p for controls in those with partial Mayo score). Only medication non-adherence was significantly more frequent in the flare group than in the control group (48.5% vs 29.4%, P = 0.03) and remained significant on multivariate analysis (OR = 2.86, 95%CI: 1.33-6.18). On multivariate regression analysis, immunomodulator use was found to be associated with significantly lower rates of flare (OR = 0.40, 95%CI: 0.19-0.86). CONCLUSION In a study of potential triggers for IBD flares, medication non-adherence was significantly associated with flares. These findings are incentive to improve medication adherence.

Sa1937 Continuous Bile Acid Exposure Is a Risk Factor for Development of Reactive Gastropathy

and the thromboxane (TX) A2 antagonistic action, although the exact mechanism remains unexplored. In the present study, we examined the effects of egualen against gastric lesions induced by ischemia/reperfusion (I/R) as well as double antithrombotic therapy with lowdose aspirin (ASA) plus clopidogrel, and small intestinal lesions induced by loxoprofen in rats and investigated the possible mechanisms involved in the protective action. Methods: Male SD rats were used under urethane anesthesia (gastric I/R and bleeding models) or conscious (intestinal lesion model) conditions. I/Rinduced gastric injury was produced in mice by clamping celiac artery for 30 min, followed by reperfusion for 60 min. Egualen, ozagurel (a TXA2 synthase inhibitor) or seratrodast (a TXA2 antagonist) was given introduodenally (ID) 60 min before ischemia/reperfusion. Gastric bleeding was induced by luminal perfusion with 25 mM ASA+50 mM HCl for 2 h in the presence of clopidogrel (30 mg/kg). Egualen was given ID 60 min before ASA perfusion, while PGE2 was given IV 30 min before. To produce small intestinal lesions the animals were given loxoprofen (60 mg/kg) PO and killed 24 h later. Egualen was given PO 30 min before and 6 h after loxoprofen. Results: The severity of I/R-induced gastric lesions was significantly reduced by pretreatment with egualen, in addition to ozagrel and seratrodast, suggesting the involvement of the TXA2 antagonistic action in the protective effect of egualen in this model. Perfusion of the stomach with ASA in the presence of clopidogrel produced gastric lesions with severe bleeding. Egualen significantly reduced the gastric ulcerogenic and bleeding responses to the antiplatelet therapy, similar to PGE2. On the other hand, loxoprofen induced multiple lesions in the small intestine, accompanied by a decrease in mucus secretion, an increase in bacterial invasion and iNOS expression. Egualen prevented the development of small intestinal lesions, together with increase of mucus secretion and suppression of bacterial invasion and iNOS expression. Conclusion: These results suggest that egualen has prophylactic effect against a variety of gastrointestinal lesions, probably through its characteristic pharmacological properties, such as the TXA2 antagonistic action and local mucosal protection in the stomach, and suppression of bacterial invasion due to the increased mucus secretion in the small intestine.

Su1781 Reactive Gastropathy and Correlation With Medications, Helicobacter pylori and Gastric Inflammation

INTRODUCTION: Studies show that single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID)-metabolising enzymes (mainly CYP2C9 & CYP2C8) may predispose NSAID-users to peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results to date have been inconclusive due to small sample sizes and different study designs. METHODS: We hypothesised that the eight closely-linked clinically important SNPs in the CYP2C family of genes, namely CYP2C8*3 (rs11572080 & rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 may predispose to PUD via impaired NSAID metabolism as well as other potentially important mechanisms such as metabolism of arachidonic acid (AA) and protonpump inhibitors (PPIs). Subjects endoscoped for suspected PUD/UGIB at 13 hospitals in the UK between 2005 and 2011 were recruited and interviewed using a structured questionnaire. Recruits were categorised as either NSAID-users (use within 2 weeks) or non-users (no use within 3 months). UGIB was defined as haematemesis, melaena or anaemia, and endoscopic stigmata of recent bleeding. H. pylori status was ascertained in most subjects. Following extraction of genomic DNA, genotyping was performed by KBioscience Ltd (UK). Logistic regression analysis was used to test for association between each SNP and risk of PUD/ UGIB. Interaction terms were introduced to determine whether any observed genetic effects were influenced by factors including type of NSAID, PPI use and gender. RESULTS: Overall,1246 white patients were recruited and categorised as follows: 485 (39%) PUD+/NSAID+; 357 (29%) PUD+/NSAID-; 125 (10%) PUD-/NSAID+; 280 (22%) PUD-/NSAID-. Seven SNPs were included in the final analysis (CYP2C19*3 was monomorphic and excluded). All SNPs were in Hardy-Weinberg equilibrium. Logistic regression analysis of cases (PUD+; n=842) and controls (PUD-; n=405), assuming an additive mode of inheritance at each SNP, showed that only CYP2C19*17 was significantly associated with PUD (p=0.006), with suggestion of an allele-dose effect, even on classifying cases as those using only CYP2C9/CYP2C8substrate NSAIDs (p=0.005). Post-hoc analysis showed no interaction between CYP2C19*17 and NSAID type, PPI use or gender. Subgroup analysis per ulcer type showed CYP2C19*17 was significantly associated with risk of gastric ulcers (p=0.02), whilst only rs11572080 was associated with risk of duodenal ulcers (p=0.04). No SNPs were associated with UGIB. CONCLUSION: Possession of CYP2C19*17 allele is associated with PUD, especially gastric ulcers, regardless of aetiology. We postulate that this could be through its effect on the metabolism of AA or other endogenous substances, leading to impairment of gastrointestinal mucosal defences. Further studies are needed to correlate the functional consequences of CYP2C19*17 in the pathogenesis of PUD.