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Abstract

Previous studies of probiotic formulations of single species of bacteria did not show efficacy in preventing the recurrence of Crohn's disease after surgery. In this issue, Fedorak et al investigated VSL#3, a mixture of 8 different bacterial probiotic species, to prevent Crohn's disease recurrence following surgery in a multi-center, randomized, double blind placebo-controlled trial. Within 30 days of ileo-colonic resection and re-anastomosis, 59 patients with Crohn's disease were randomly assigned to groups given 1 sachet of VSL#3 (900 billion viable bacteria, comprising 4 strains of Lactobacillus, 3 strains of Bifidobacterium, and 1 strain of Streptococcus salivarius subspecies Thermophiles) or matching placebo (n = 60). Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis. Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365. At day 90, the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 (9.3%) or placebo (15.7%); P = .19. The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0% in the early VSL#3 group and 26.7% in the late VSL#3 group (P = .09). However, patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared to placebo at day 90 (P < .05) thus indicating that this probiotic may need to be further investigated for prevention of Crohn's disease recurrence. Therefore despite the appeal and wide spread use of probiotics, solid evidence for their efficacy in Crohn’s disease is lacking. This article is highlighted by an editorial by R. Balfour Sartor (page 936). See page 928. Practice guidelines recommend the use of pH-impedance to optimize the management of patients with refractory or difficult treat suspected reflux symptoms. However, the clinical utility of pH-impedance monitoring on or off antisecretory therapy remains unclear. Patel et al prospectively evaluated a cohort of patients between 2005 and 2010 following pH-impedance monitoring to determine predictors of symptom improvement. Symptom questionnaires assessed dominant symptom intensity (DSI) and global symptom severity (GSS) at baseline and on follow-up. Acid exposure time (AET), reflux exposure time (RET, duration of impedance drop 5 cm above lower esophageal sphincter, reported as % time similar to AET), symptom-reflux correlation (symptom index [SI]; symptom association probability [SAP]), and total numbers of reflux events were extracted. A total of 187 subjects (mean age 53.8 years, 70.6% female) fulfilled inclusion criteria; 49.7% were tested on PPI therapy and 68.4% were managed medically. After 39.9 average follow-up, both DSI and GSS significantly improved (P < .05). Abnormal AET predicted DSI and GSS improvement (P ≤ .049 for each comparison); RET and SAP from impedance-detected reflux events (P ≤ .03) were also predictive. On multivariate analysis, abnormal AET consistently predicted symptomatic outcome; other predictors included impedance detected SAP, older age, and testing off PPI (Figure 1). The authors concluded that elevated AET offers the best predictive value for symptomatic improvement from antireflux therapy, complemented by impedance-based symptom reflux correlation. Both these parameters are best evaluated off antisecretory therapy. Short of randomized trials, this study provides the best available evidence to guide practice in this difficult area. This article is highlighted by an editorial by Michael F. Vaezi (page 892). See page 884. A previous meta-analysis demonstrated an elevated risk of lymphoma associated with thiopurine therapy for inflammatory bowel disease (IBD). Twelve additional studies have been published subsequently. In this issue, Kotlyar et al. estimated the relative risk of lymphoma in IBD patients exposed to thiopurines, and compared relative risks derived from population-based studies with that of referral center-based studies. They also examined active (vs past) and variations related to gender, age, or duration of use. After a comprehensive search, 18 studies met inclusion criteria. Compared to referral center studies, population-based studies of IBD patients show a lower but significantly elevated risk of lymphoma with use of thiopurines; the standardized incidence ratio (SIR) for lymphoma was 4.49 (95% CI, 2.81–7.17), varying from 2.43 (1.50–3.92) among 8 population studies to 9.16 (5.03–16.7) among 10 referral studies (Figure 2). The increased risk does not appear to persist after discontinuation of therapy. In population studies, an elevated risk (SIR = 5.71; 95% CI = 3.72-10.1) was seen in current users but not in former users (SIR = 1.42; 95% CI = 0.86–2.34). Those under 30 also have the highest relative risk compared to the general population (SIR = 6.99, CI = 2.99–16.4), and young men are at particularly high risk. The absolute risk was highest in patients over 50 with a number needed to harm of about 1 in 377 patients exposed per year. For patients of all ages and genders, the risk of lymphoma needs to be weighed against the potential benefits of therapy. See page 847. Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Azathioprine and 6-Mercaptopurine: A Meta-analysisClinical Gastroenterology and HepatologyVol. 13Issue 5PreviewThiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk of lymphoma in patients with IBD exposed to thiopurines and compared relative risk values derived from population-based studies with those from referral center–based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma. Full-Text PDF The Probiotic VSL#3 Has Anti-inflammatory Effects and Could Reduce Endoscopic Recurrence After Surgery for Crohn's DiseaseClinical Gastroenterology and HepatologyVol. 13Issue 5PreviewProbiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn’s disease after surgery. We investigated the ability of VSL#3, a mixture of 8 different bacterial probiotic species, to prevent Crohn’s disease recurrence after surgery in a multicenter, randomized, double-blind, placebo-controlled trial. Full-Text PDF Parameters on Esophageal pH-Impedance Monitoring That Predict Outcomes of Patients With Gastroesophageal Reflux DiseaseClinical Gastroenterology and HepatologyVol. 13Issue 5PreviewpH-impedance monitoring detects acid and nonacid reflux events, but little is known about which parameters predict outcomes of different management strategies. We evaluated a cohort of medically and surgically managed patients after pH-impedance monitoring to identify factors that predict symptom improvement after therapy. Full-Text PDF