Capsule endoscopy is superior to small-bowel follow-through and equivalent to ileocolonoscopy in suspected Crohn's disease.

BACKGROUND & AIMS: Evaluation of the small intestine for inflammation has traditionally relied on small-bowel follow-through (SBFT), but multiple studies have demonstrated its low diagnostic accuracy. Capsule endoscopy (CE) transmits high-quality images of the small intestinal mucosa; it can be used to visualize the entire length of the small bowel and much of the mucosa. We compared the diagnostic yields of CE vs SBFT in a prospective study of patients with suspected small-bowel Crohn's disease. METHODS: Eighty patients with signs and/or symptoms of small-bowel Crohn's disease (age, 10-65 years) underwent CE, followed by SBFT and ileocolonoscopy. Readers were blinded to other test results. The primary outcome was the diagnostic yield for inflammatory lesions found with CE before ileocolonoscopy compared with SBFT and ileocolonoscopy. A secondary outcome was the incremental diagnostic yield of CE compared with ileocolonoscopy and CE compared with SBFT. RESULTS: The combination of CE and ileocolonoscopy detected 107 of 110 inflammatory lesions (97.3%), whereas the combination of SBFT and ileocolonoscopy detected only 63 lesions (57.3%) (P < .001). The diagnostic yield of CE compared with ileocolonoscopy was not different (P = .09). The diagnostic yield was higher for CE than for SBFT (P < .001). Of the 80 patients with suspected Crohn's disease, 25 (31.3%) had the diagnosis confirmed. Eleven were diagnosed by CE findings alone and 5 by ileocolonoscopy findings alone. In the remaining 9 patients, diagnostic findings were identified by at least 2 of the 3 modalities. No diagnoses were made on the basis of SBFT findings alone. CONCLUSIONS: CE was better than SBFT and equivalent to ileocolonoscopy in detecting small-bowel inflammation. Although ileocolonoscopy remains the initial diagnostic test of choice, CE is safe and can establish the diagnosis of Crohn's disease in patients when ileocolonoscopy results are negative or the terminal ileum cannot be evaluated. ClinicalTrials.gov Number: NCT00487396.

Innate immune receptor genetic polymorphisms in pouchitis: is CARD15 a susceptibility factor?

BACKGROUND: Pouchitis is a frequent complication after ileal pouch-anal anastamosis (IPAA) for ulcerative colitis (UC). The aim of this study was to determine whether genetic polymorphisms in the innate immune receptors toll-like receptor (TLR)4 and caspase activation and recruitment domain family member 15 (CARD15) genes are associated with pouchitis. METHODS: From a retrospectively ascertained cohort of patients with UC 5 to 12 years after IPAA (n = 101), subjects were classified into 3 groups: no pouchitis (n = 52); 1 to 2 episodes per year (n = 11), and more than 2 episodes per year (n = 38). Single nucleotide polymorphisms in the tlr4 gene (D299G, T399I) were determined by a real-time polymerase chain reaction-based fluorogenic probe technique; and card15 polymorphisms (L1007fsinsC, R702W, G908R) were determined by pyrosequencing. RESULTS: Pouchitis affected 49% (49/101) of the study population. No correlation between pouchitis and the presence of TLR4 polymorphisms was found. The percentage of patients who harbored CARD15 mutations was significantly higher in patients with pouchitis than in patients without pouchitis (18% versus 8%; P < 0.05); 24% of pouchitis patients with more than 2 episodes per year harbored CARD15 mutations (P < 0.01 compared with the no pouchitis group). The CARD15 insertion mutation L1007fsinsC was present in 14% of patients with pouchitis and in 0% without pouchitis (P < 0.05). All patients who carried L1007fsinsC developed more than 2 episodes per year. CONCLUSIONS: CARD15 polymorphisms are seen in greater frequency in patients with pouchitis after IPAA for UC. These findings, if borne out in prospective analyses, suggest that CARD15 mutations, particularly L1007fsinsC, may predispose to the development of pouchitis after IPAA for UC.

Therapeutic options in the management of strictures in Crohn's disease.

Intestinal strictures are a commonly encountered problem in patients with Crohn's disease. Endoscopic management with hydrostatic balloon dilation is an effective alternative to surgery in patients with endoscopically accessible lesions that are shorter than 7-8 cm. Endoscopic balloon dilation is the preferred initial modality in anastomotic strictures. The presence of inflammation near the stricture should not be considered a contraindication to dilation, and intralesional steroid injection should be considered in these patients with inflammation present in the area of the stricture. Further technological developments in endoscopes and balloon dilators may allow for broader application of these techniques.

Predictors and outcome of gastrointestinal complications in patients undergoing cardiac surgery.

OBJECTIVE: To determine the incidence and independent predictors of gastrointestinal complications (GICs) following cardiac surgery. SUMMARY BACKGROUND DATA: Gastrointestinal ischemia and hemorrhage represent a rare but devastating complication following heart surgery. The profile of patients referred for cardiac surgery has changed during the last decade, questioning the validity of previously reported incidence and risk factors. METHODS: We retrospectively analyzed prospectively collected data from 4819 patients undergoing cardiac surgery between 1998 and 2004. Patients with GICs were compared with the entire patient population. Study endpoints were mortality, postoperative morbidities, and long-term survival. RESULTS: GICs occurred in 51 (1.1%) patients. Etiologies were intestinal ischemia (n = 30; 59%) and hemorrhage (n = 21; 41%). The incidence decreased during the study period (1998-2001: 1.3%, 2002-2004: 0.7%; P = 0.04). The incidence per type of procedure was as follows: coronary artery bypass grafting (CABG)/valve (2.4%), aortic surgery (1.7%), valve surgery (1.0%), and CABG (0.5%; P = 0.001). Multivariate analysis revealed age (odds ratio [OR] = 2.1), myocardial infarction (OR = 2.5), CHF (OR = 2.4), hemodynamic instability (OR = 2.8), cardiopulmonary bypass time >120 minutes (OR = 6.2), peripheral vascular disease (OR = 2.2), renal (OR = 3.2), and hepatic failure (OR = 10.8) as independent predictors of GICs. The overall hospital mortality among patients with GICs was 33%. Long-term survival was significantly decreased in patients with GICs compared with the control group. CONCLUSIONS: Gastrointestinal complications following cardiac surgery remain rare with an incidence <1% in a contemporary series. The key to a lower incidence of GICs lies in systematic application of preventive measures and new advances in intraoperative management. Identification of independent risk factors would facilitate the determination of patients who would benefit from additional perioperative monitoring. Future resources should therefore be redirected to mitigate GICs in high-risk patients.

Immunomodulator Therapy in Inflammatory Bowel Disease.

6-Mercaptopurine and its prodrug counterpart, azathioprine, have proven efficacy in the induction and maintenance of remission, fistula closure, and steroid sparing in patients with Crohn's disease. Long-term follow-up has demonstrated the safety of the purine analogues, with no increased risk of malignancy. For patients with Crohn's disease intolerant or unresponsive to azathioprine or 6-mercaptopurine, methotrexate has emerged as an effective alternative. In patients with severe ulcerative colitis, intravenous cyclosporine is highly efficacious in the short term, and with the addition of azathioprine or 6-mercaptopurine to oral cyclosporine, long-term remission rates of 60% to 70% can be achieved. Azathioprine or 6-mercaptopurine therapy is effective in patients with steroid-dependent or steroid-refractory colitis and is valuable in maintaining remission. Neither methotrexate nor cyclosporine has been shown to be effective for maintenance therapy in patients with ulcerative colitis. Current data are insufficient to recommend routine use of genetic or enzymatic testing of thiopurine methyltransferase or measurements of blood 6-thioguanine metabolites to guide 6-mercaptopurine or azathioprine dosing.

Are pANCA, ASCA, or cytokine gene polymorphisms associated with pouchitis? Long-term follow-up in 102 ulcerative colitis patients.

OBJECTIVE: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for ulcerative colitis. This study aims to analyze the frequency and characteristics of pouchitis in long-term follow-up in a large population, and to determine whether a significant association exists between five immunogenetic markers and pouchitis. METHODS: From a population of over 500 ulcerative colitis patients who had undergone ileal pouch-anal anastamosis 5-12 yr earlier, 102 subjects participated in the study. Using clinical data obtained from interviews and chart reviews, patients were classified into three groups: no pouchitis; 1-2 episodes per year; and >2 episodes per year. Coded sera from the patients were analyzed for ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies and Crohn's disease-associated anti-saccharomyces cerevesiae antibodies. Interleukin-1 receptor antagonist, tumor necrosis factor (TNF), and lymphotoxin beta (lymphotoxin) polymorphisms were also analyzed. RESULTS: Pouchitis affected 49% of the study population. Antineutrophil cytoplasmic antibodies, anti-saccharomyces cerevesiae antibodies, and lymphotoxin-beta polymorphisms were not associated with pouchitis. Carriage of interleukin-1 receptor antagonist allele 2 was significantly greater among those without pouchitis than those with pouchitis. Patients without pouchitis had a significantly greater carriage rate of TNF allele 2. CONCLUSIONS: Perinuclear antineutrophil cytoplasmic antibodies and anti-saccharomyces cerevesiae antibodies are not correlated with pouchitis, but interleukin-1 receptor antagonist and TNF may play a role in its development. Further evaluation of these markers in pouchitis will require larger populations, long-term prospective observation, and studies that correlate polymorphisms with specific immunologic functions.