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Background: We investigated symptoms and tests performed prior to a formal diagnosis of Crohn's disease and the reasons for diagnostic delay., Methods: Consecutive patients recently diagnosed with Crohn's disease were enrolled between October 2012 and November 2013. Clinical data, symptoms including Rome III criteria at onset and at diagnosis, location and disease phenotype were recorded. Faecal calprotectin, radiological and endoscopic examinations performed prior to diagnosis were analysed. Diagnostic delay, stratified into tertiles and median time, was analysed using parametric and nonparametric tests., Results: 83 patients (49.4% males, median age 31 years) were enrolled. The median diagnostic delay was 8 (0-324) months. Twenty-six patients did not consult a general practitioner until diagnosis (31.3%), 18 presented to the emergency department (21.7%) and 8 directly to a gastroenterologist (9.6%). Diagnostic delay was not associated with specific symptoms. However, patients with bloating at presentation had a longer delay compared to those who did not (median, 6.1 vs. 16.8 months, respectively; p=0.016). Nineteen patients underwent incomplete ileocolonoscopies (22.9%) and 7 had no biopsies (8.4%), with a consequent diagnostic delay (median, 24 and 24 vs. 6 months, respectively; p=0.025 and p=0.008)., Conclusion: Diagnostic delay for Crohn's disease is significantly associated with incomplete ileocolonoscopies, but not with symptoms, except bloating at presentation., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: ABO encodes a glycosyltranferase which determines the major human histo-blood group. The FUT2 fucosyltransferase allows expression of ABO antigens on the gastrointestinal mucosa and in bodily secretions (secretor phenotype). A nonsense allele in FUT2 represents a susceptibility variant for Crohn's disease, and both the secretor and ABO blood group status affect the composition of the gut microbiota. Thus, we evaluated if variants in ABO might represent good candidates as Crohn's disease susceptibility loci., Methods: We recruited two case-control cohorts, from Italy (n=1301) and Belgium (n=2331). Subjects were genotyped for one SNP in FUT2 and two variants in ABO., Results: No effect on Crohn's disease risk was detected for ABO variants, whereas an association was observed between the FUT2 polymorphism and Crohn's disease susceptibility in the Belgian sample, but not in the Italian cohort. The effect of histo-blood groups was evaluated using group O as the reference. Most non-O groups had odds ratios (ORs) higher than 1 in both cohorts, and combined analysis of the two samples indicated a predisposing effect for the A and B groups (OR=1.17, 95% CI: 1.02-1.32 and OR=1.33, 95% CI: 1.09-1.58, respectively). In Crohn's disease patients, the non-O blood group and the non-secretor status were associated with higher risk of developing a stricturing or penetrating disease., Conclusions: ABO histo-blood group might confer susceptibility to Crohn's disease and modulate disease severity., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: To assess the accuracy of transperineal ultrasound (TPUS), in comparison with magnetic resonance imaging (MRI), in classifying perianal Crohn's disease (CD) according to Parks' classification and the American Gastroenterological Association criteria., Methods: Fifty-nine consecutive patients with confirmed or suspected perianal CD underwent TPUS and MRI within 10 days. An independent expert surgical evaluation, which took into account proctological and MRI findings, was used as the gold standard. Fistulae and perianal disease were classified according to Parks' classification and American Gastroenterological Association criteria, respectively., Results: Forty-six patients showed 64 fistulae (9 intersphincteric, 34 transsphincteric, 2 suprasphincteric, 9 extrasphincteric, and 10 anovaginal) and 23 abscesses were also found. Fifty-one of 54 perianal fistulae (per-lesion sensitivity: 94.4%) and 9 of 10 anovaginal fistulae (sensitivity: 90.0%) were detected and 58 were correctly classified by TPUS (sensitivity: 90.6%; positive predictive value: 93.4%). Overall, TPUS correctly detected and classified the fistulae in 89% of patients and the agreement for classifying perianal fistulae between TPUS and MRI was excellent (K value: 0.783). In contrast, 11 of 23 abscesses were correctly diagnosed by TPUS (sensitivity: 47.8%); although 14 abscesses were diagnosed by TPUS, only 11 were confirmed by MRI (positive predictive value: 78.6%). Overall, TPUS correctly detected and classified fistulae and associated abscesses in 67.3% of patients. Agreement between MRI and TPUS in discriminating simple (15) and complex (29) perianal disease was fairly good (K value: 0.57)., Conclusions: TPUS is a simple and accurate diagnostic method for classifying perianal fistulae in CD and could be used for the preliminary assessment and follow-up of perianal CD.

Previous studies indicated that a few risk variants for autoimmune diseases are subject to pathogen-driven selection. Nonetheless, the proportion of risk loci that has been targeted by pathogens and the type of infectious agent(s) that exerted the strongest pressure remain to be evaluated. We assessed whether different pathogens exerted a pressure on known Crohn's disease (CD) risk variants and demonstrate that these single-nucleotide polymorphisms (SNPs) are preferential targets of protozoa-driven selection (P = 0.008). In particular, 19% of SNPs associated with CD have been subject to protozoa-driven selective pressure. Analysis of P values from genome-wide association studies (GWASs) and meta-analyses indicated that protozoan-selected SNPs display significantly stronger association with CD compared with nonselected variants. This same behavior was not observed for GWASs of other autoimmune diseases. Thus, we integrated selection signatures and meta-analysis results to prioritize five genic SNPs for replication in an Italian cohort. Three SNPs were significantly associated with CD risk, and combination with meta-analysis results yielded P values < 4 × 10(-6). The bona fide risk alleles are located in ARHGEF2, an interactor of NOD2, NSF, a gene involved in autophagy, and HEBP1, encoding a possible mediator of inflammation. Pathway analysis indicated that ARHGEF2 and NSF participate in a molecular network, which also contains VAMP3 (previously associated to CD) and is centered around miR-31 (known to be disregulated in CD). Thus, we show that protozoa-driven selective pressure had a major role in shaping predisposition to CD. We next used this information for the identification of three bona fide novel susceptibility loci.

Background and Methods: Portal vein thrombosis (PVT) has been reported as a complication of IBD in some case reports. We describe the presentation, diagnostic approaches, underlying risks factors and clinical outcome of 8 IBD patients with PVT. CASE-SERIES: The patients presented with partial PVT (4 patients) or portal cavernoma. Five patients had undergone surgery. In 2 patients portal biliopathy was diagnosed after detection of PVT. In 4 patients, the diagnosis of PVT was made while IBD was in remission. Five patients showed at least one risk factor for hypercoagulability: lupus anti-coagulant (one patient), increased von Willebrand factor (2 patients) or homocysteine levels (4 patients). Four patients received anticoagulant therapy for 6 months. None experienced other thrombotic events during a median of 5 years (range 2-8 years)., Conclusion: PVT is a potential complication of IBD, usually associated with acquired or inherited risks factors for hypercoagulability and with a benign outcome., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Thiopurines are the most commonly used immunomodulatory drugs in inflammatory bowel diseases., Aim: To evaluate the use, the therapeutic and safety profiles of thiopurines in a large sample of IBD patients., Methods: We reviewed 3641 case histories of IBD patients. Thiopurines were prescribed in 582 patients (16.0%); the analysis was performed on the 553 (267 ulcerative colitis, 286 Crohn's disease) with exhaustive clinical data., Results: The main indications for treatment were steroid-dependence (328/553, 59.3%) and steroid-resistance (113/553, 20.7%). Thiopurines were started when CD were younger than UC patients (p<0.001) but earlier from diagnosis in UC than in CD patients (p=0.003). Efficacy was defined as optimal (258/553, 46.6%), partial (108/553, 19.5%), absent (85/553, 15.4%) and not assessable (102/553, 18.4%). Efficacy was independent of disease type, location/extension or duration and age at starting. Side effects were observed in 151/553 (27.3%) patients, leading to drug discontinuation in 101 (18.3%). 15 out of the 130 (11.5%) patients who took thiopurines for more than 4 years relapsed, more frequently in CD than in UC (OR=3.67 95% C.I. 0.98-13.69; p=0.053)., Conclusions: Thiopurines confirm their clinical usefulness and acceptable safety profile in managing complicated IBD patients. The majority of patients treated for longer than 4 years maintain response. No clinical and demographic predictive factors for efficacy and side effects were identified.

The investigation of small bowel morphology is often mandatory in many patients with Crohn's disease. Traditional radiological techniques (small bowel enteroclysis and small bowel follow-through) have long been the only suitable methods for this purpose. In recent years, several alternative imaging techniques have been proposed. To review the most recent advances in imaging studies of the small bowel, with particular reference to their possible application in Crohn's disease, we conducted a complete review of the most important studies in which traditional and newer imaging methods were performed and compared in patients with Crohn's disease. Several radiological and endoscopic techniques are now available for the study of the small bowel; each of them is characterized by a distinct profile of favourable and unfavourable features. In some cases, they may also be used as complementary rather than alternative techniques. In everyday practice, the choice of the technique to be used stands upon its availability and a careful evaluation of diagnostic accuracy, clinical usefulness, safety and cost. The recent development of innovative imaging techniques has opened a new and exciting area in the exploration of the small bowel in Crohn's disease patients.

Background and Aim: Inflammatory bowel diseases (IBD) commonly affect women during the reproductive years. The aim of the present study was to evaluate the reproductive histories of patients with ulcerative colitis (UC) and Crohn's disease (CD) considering pregnancies occurring before and after the diagnosis., Method: Case-control study evaluating IBD patients, interviewed by questionnaire about outcome of pregnancy and course of disease., Results: A total of 502 pregnancies from 199 patients in the prediagnosis group and 121 pregnancies from 90 patients in the post-diagnosis group were respectively compared with 996 and 204 pregnancies recorded in a control population. In prediagnosis pregnancies, CD was associated with increased risk of preterm delivery (odds ratio [OR] 4.62, 95% confidence interval [CI] 2.77-7.73; P < 0.001 vs controls and OR 3.52, 95% CI 1.75-7.07; P < 0.001 vs UC) and lower birthweight (P < 0.001 vs UC and controls). In post-diagnosis pregnancies, the rate of live births was lower, but not statistically significant in IBD (OR 0.22, 95% CI 0.04-1.25; P = 0.08) and the birthweight was significantly lower in CD than in UC (P < 0.03) and in controls (P < 0.02). In post-diagnosis pregnancies, a higher incidence of congenital abnormalities was found in IBD patients (5.5% vs 0.0%). The spontaneous abortion rate and therapeutic abortions were significantly higher in post than in prediagnosis pregnancies. Neither disease activity at conception nor treatment appeared to influence the outcome of pregnancy., Conclusions: CD in the preclinical phase has some influence on pregnancy. In patients with IBD our data suggest that conception should not be discouraged. However, because of a modest increase in mild congenital abnormalities and abortions rates, pregnancy in IBD patients should be closely monitored.

Background: Capsule enteroscopy is a non-invasive diagnostic tool for the study of the small bowel. Due to the risk of capsule retention, capsule enteroscopy is contraindicated in patients with suspected small bowel strictures. The Given Patency Capsule is a disintegration time-controlled capsule developed to identify patients with strictures that may cause capsule enteroscopy retention. The presence of the patency capsule within the patient's body can be detected by a radio-frequency scanner., Aim of the Study: To evaluate safety and usefulness of the patency capsule in preventing capsule retention in patients at high risk., Patients and Methods: Thirty-two patients were studied. Indications for patency capsule were: (A) Crohn's disease (18), (B) previous intestinal surgery (7), (C) previous obstruction (1), A+B (3), A+C (1), B+C (2). Patients were evaluated with the scanner at 72 h from ingestion., Results: At 72 h, 24 patients had already excreted the intact capsule in the stool. Of these, two experienced abdominal pain during capsule passage. In the other eight patients, the scanner detected the presence of the patency capsule. Four of them excreted the capsule intact in the stool after 72-96 h, the remaining four never found the capsule in the stool. The 26 patients who excreted the patency capsule intact without experiencing abdominal pain were deemed eligible for the capsule enteroscopy procedure, which was performed uneventfully in the 25 who agreed to undergo the examination., Conclusions: The patency capsule is useful to identify, among patients at high risk, those who can be submitted to capsule enteroscopy without risks of capsule retention.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Background: It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated., Aim: To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor., Methods: We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 +/- 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs)., Results: Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6-9.2; P = 0.003). Kaplan-Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0)., Conclusions: In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.

Background/aims: Measurement of health related quality of life (HRQoL) is a new tool to evaluate patients with inflammatory bowel disease (IBD). The aims of this study were to verify reliability and responsiveness of a disease-specific questionnaire [Italian Questionnaire on Quality of Life (IQQoL)], and to assess the relationship between clinical and demographic variables and HRQoL in IBD patients., Methodology: The IQQoL was submitted to all IBD patients consecutively seen at eight participating Hospitals, and re-administered at follow-up visits. The IQQoL covers intestinal and systemic symptoms, emotional and social function. The higher the score, the worse the HRQoL., Results: 249 patients were enrolled, 106 with Crohn's disease (CD) and 143 with ulcerative colitis (UC). IQQoL was re-administered to 134 patients: 98 with unchanged, 17 with worsened and 19 with improved disease activity. The IQQoL was stable over time in patients with stable clinical conditions, and very responsive to change both in patients with improved and worsened disease activity. HRQoL was inversely correlated with disease activity, both in CD and UC. Perception of HRQoL was significantly worse in women than in men., Conclusions: The IQQoL is a reliable and responsive instrument to assess HRQoL in IBD patients. Active disease is related to poor HRQoL perception. In CD, women, mainly if young, have a worse HRQoL perception than men.

Background: Coagulation Factor XIII is implicated in fibrin stabilization and wound healing. Plasma levels of Factor XIII are reduced in inflammatory bowel disease patients; recently, a valine 34 to leucine polymorphism of the Factor XIII-A subunit gene with a defined protective effect against thrombosis and as yet undetermined effect on wound healing has been described., Aim: To evaluate Val34Leu Factor XIII polymorphism distribution and to find possible correlations with clinical features in Italian inflammatory bowel disease patients., Study Population: A total of 152 inflammatory bowel disease patients, 90 with ulcerative colitis and 62 with Crohn's disease and 130 healthy volunteers were studied., Methods: Val34Leu polymorphism was detected by RFLP with BsaH I. Statistical analysis was performed by means of Fisher exact test., Results: In inflammatory bowel disease, 57.2% of patients showed the wild type status, 37.5% were heterozygous and 5.3% were homozygous for the 34Leu allele; the frequency of the mutated allele was 24.0%. In controls, 66.1% of subjects showed the wild type status, 28.5% were heterozygous and 5.4% were homozygous for the 34Leu allele; the frequency of the mutated allele was 19.7%. There was no difference in genotype distribution and prevalence of the mutated allele between inflammatory bowel disease patients and controls., Conclusions: The present data do not show any differences in Val34Leu Factor XIII polymorphism distribution between inflammatory bowel disease patients and controls. The prothrombotic state described in inflammatory bowel disease patients does not depend on an altered distribution of Val34Leu Factor XIII polymorphism.

Objectives: Individuals with inflammatory bowel disease (IBD) are at increased risk for thrombosis and vitamin deficiencies. Low plasma levels of vitamin B(6) are an independent risk factor for thrombosis and may cause hyperhomocysteinemia, another recognized risk factor for thrombosis. The aim of this study was to evaluate vitamin B(6) plasma levels in IBD patients., Methods: We studied 61 IBD patients: 32 with Crohn's disease and 29 with ulcerative colitis. For each patient, three sex- and age-matched healthy control subjects were studied., Results: Median vitamin B(6) levels were significantly lower in IBD patients (22.0 pmol/L, range 3.6-231.0) than in controls (31.1 pmol/L, 3.7-363.4; p < 0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B(6) levels lower than the 5th percentile of distribution in normal controls (p < 0.05). Low vitamin B(6) levels were significantly more frequent in patients with active disease than in patients with quiescent disease (seven of 26, 26.9%, vs one of 35, 2.9%; p < 0.001). Moreover, patients with active disease had significantly lower median vitamin B(6) levels (13.4 pmol/L, range 3.6-124.0) than patients in a quiescent phase (27.0 pmol/L, 7.8-231.0; p < 0.001). Low vitamin B(6) levels were significantly correlated with serum concentrations of C-reactive protein (r = -0.36, 95% CI = -0.59 to -0.09, p < 0.01) and alpha(1)-acid-glycoprotein (r = -0.37, 95% CI = -0.59 to -0.10, p < 0.01). Hyperhomocysteinemia was more frequent in patients with low vitamin B(6) levels (three of eight, 37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There was no statistically significant correlation between vitamin B(6) and homocysteine plasma levels (r = -0.13, 95% CI = -0.37 to +0.14, p = 0.33)., Conclusions: Low vitamin B(6) plasma levels, an independent risk factor for thrombosis, are frequent in patients with IBD, especially those with active disease.

Objectives: Observations in experimental models and in human ulcerative colitis suggest that activation of the kallikrein-kinin system plays a role in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess activation of the plasma and tissue kallikrein-kinin system in Crohn's disease., Methods: We studied plasma inflammatory and contact system parameters in 36 patients with Crohn's disease and in 36 control subjects with noninflammatory GI diseases. We also obtained tissue samples from the involved intestine of 12 patients with Crohn's disease, and from normal peritumoral tissue (12 patients) and diverticulitis tissue (seven patients) as controls. Full-thickness sections were tested for intestinal tissue kallikrein reactivity with a specific antibody., Results: In Crohn's disease patients and controls, plasma levels of prekallikrein, factor XI, high molecular weight kininogen and its cleaved form were normal. Crohn's disease patients had significantly higher levels of antigen and functional Cl-inhibitor (+22%, +12%) than did controls (p = 0.005, p = 0.004). After surgical resection, antigen and functional Cl-inhibitor significantly decreased in Crohn's disease patients (-22%, -15%; p = 0.035, p = 0.006). Intestinal tissue kallikrein immunoreactivity was absent (75%) or weak (25%) in the goblet cells from Crohn's disease tissue sections but was normal in controls, with a highly significant difference in the staining score (p = 0.0001). Intestinal tissue kallikrein immunoreactivity in the interstitium was higher in Crohn's disease than in normal and diverticulitis samples (p = 0.0001 and p = 0.001, respectively)., Conclusions: Our observations suggest that intestinal tissue kallikrein is involved in the inflammatory process in Crohn's disease. The lack of contact system activation in peripheral blood might be related to the high plasma levels of Cl-inhibitor, the most important inhibitor of the contact system in the circulation.

Background: Increased levels of circulating von Willebrand factor (vWF) have been found in patients with inflammatory bowel disease (IBD); this increase may reflect either endothelial damage or systemic inflammation. Our aim was to evaluate serum vWF levels in patients with IBD and their correlation with clinical and biochemical disease activity., Methods: We evaluated serum vWF levels in 32 patients with ulcerative colitis (UC) (10 active with increased acute-phase reactants (APR), 6 active with normal APR, 16 in remission), 27 with Crohn disease (CD) (10 active, 12 quiescent, and 5 quiescent with increased APR), and 31 healthy controls., Results: Mean levels of vWF were 100.1 (standard deviation (s), 51.4) in IBD and 89.9 (s, 36.9) in controls (P = 0.33). Only five (8.47%) patients (three with active UC, one with active CD, and one with inactive CD but increased APR) showed circulating vWF levels higher than the upper limit of normal (150), compared with 1 (3.2%) of controls (P = 0.32). Among CD patients vWF levels were 80.0+/-25.4 in patients with quiescent disease and normal APR, 123.3+/-63.4 in patients with active disease (P = 0.04 versus inactive with normal APR), and 135.8+/-90.0 in patients with quiescent disease and increased APR (P = 0.059 versus inactive with normal APR). Among UC patients vWF levels were 82.7+/-35.6 in patients with quiescent disease and normal APR and 125.1+/-54.2 in those with active disease and increased APR (P = 0.002). Overall, mean vWF levels were significantly higher in patients with increased APR than in patients with normal APR (P = 0.0005) and controls (P = 0.009)., Conclusions: Our data show slight but significant increases in serum vWF levels in patients with IBD, which are correlated with signs of systemic inflammation.

Background: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment., Aim: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease., Methods: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal., Results: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease., Conclusions: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

We evaluate the periodicity in relapses of ulcerative colitis and Crohn's disease in this multicenter prospective study. In 275 relapses among 184 patients with inflammatory bowel disease, a statistically significant biphasic annual periodicity, with peaks in the spring and autumn, was documented only for ulcerative colitis relapses (p = 0.006). This finding may be important in understanding relapse risk factors and in terms of prevention.

Background/aims: Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery., Methods: In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed., Results: Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1., Conclusions: This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.

Fifty patients with ulcerative colitis, 24 with Crohn's disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twenty-two percent of ulcerative colitis patients, 29% of Crohn's disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohn's disease patients and 6% of controls (P less than 0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients.

A large number of hemostasis measurements complications were performed in 20 patients with inflammatory bowel disease; whose changes have been associated with an increased risk of thromboembolic. Of the 20 patients, 9 (45%) had one or more changes suggestive of activation of the hemostatic system. Such changes were more frequently observed in patients with active disease. Two patients had changes in the fibrinolytic system (high plasminogen activator inhibitor-1 levels) and 2 in the natural anticoagulants (low antithrombin III activity). Nine patients had increased plasma fibrinogen levels and 6 patients had slightly increased levels of anticardiolipin antibodies. Most of the changes observed were not related to the type, location or activity of the disease. These data show that various biochemical abnormalities may be found in patients with inflammatory bowel disease, which may account for their increased risk of thrombosis, and suggest that multiple mechanisms may interact in determining such complications.