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The goals of the Baveno workshops were to develop consensus definitions of key events related to portal hypertension and variceal bleeding, and to produce guidelines to facilitate the conduct and reporting of clinical trials. The consensus definitions concern the diagnosis of active bleeding, failure to control bleeding, the criteria to distinguish continuing bleeding from rebleeding, and the means of assessing failure to prevent rebleeding. The guidelines concern the timing of diagnostic endoscopy, the policy for blood volume restitution, the measures to prevent infection and encephalopathy, and the treatment options for acute bleeding, as well as primary and secondary prophylaxis. The intention of the experts who developed the guidelines was that, as feedback from their practical application develops, they should be adapted to better fit the practical needs. The applicability of the Baveno definitions has been evaluated in a study where the definitions of clinically significant bleeding, failure to control bleeding, the time frame for the acute bleeding episode and the definition of rebleeding were tested. The main criticism raised in this study was that tachycardia, one of the criteria that define failure to control bleeding, was misleading in 15% of patients who had the symptom but were not bleeding. [ABSTRACT FROM AUTHOR]

Variceal haemorrhage is the most serious complication of portal hypertension and is associated with a high mortality rate. The first stage of treatment is to stabilize the patient, followed by emergency diagnostic endoscopy to identify the source of the bleeding. If active variceal bleeding is found, endoscopic intervention is performed to induce haemostasis. The endoscopic techniques commonly used to treat bleeding gastro-oesophageal varices include injection sclerotherapy and band ligation. Sclerotherapy achieves haemostasis through the induction of thrombosis or by external compression of the vessel and should be performed during diagnostic endoscopy. Band ligation achieves haemostasis by physical constriction of the varix. Band ligation may be less effective than sclerotherapy in the treatment of actively bleeding oesophageal varices and is therefore recommended for subsequent elective treatment of nonbleeding varices. However, such techniques are difficult to perform during active bleeding. This has prompted the search for improved treatment protocols. Vasoactive drugs which lower portal hypertension have been administered before, during and after endoscopy and may offer an improvement in treatment. Data from several trials have suggested that pharmacotherapy in combination with endoscopic intervention is more effective than endoscopic treatment alone. Furthermore, pharmacotherapy continued for 5 days following endoscopy significantly reduces the incidence of variceal rebleeding. A strict regimen for emergency endoscopy should be used with sclerotherapy forming the basis of treatment—administered in combination with pharmacotherapy, to optimize clinical outcome. However, there is still debate concerning what is the most effective drug for treating variceal haemorrhage. [ABSTRACT FROM AUTHOR]

Describes a study of 447 Italian patients with well-compensated cirrhosis to assess the prevalence, incidence and natural history of heptocellular carcinoma, to determine the rate of detection of resectable tumors and to evaluate the final outcomeof patients with resectable tumors treated surgically. Background; Methods; Results; Conclusions.

Describes the isolation and characterization of a defective aldolase B gene from a patient with hereditary fructose intolerance. Subjects and methods; Results; Discussion.

A response by M. Colombo and R. de Franchis to a letter to the editor on their article about hepatocellular carcinoma is presented.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensusbased guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting. [ABSTRACT FROM AUTHOR]

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensusbased guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting. [ABSTRACT FROM AUTHOR]

Background & Aims: The definition of failure to control bleeding agreed upon at the Baveno IV consensus meeting, included the Adjusted Blood Requirement Index [ABRI: number of blood units/(final−initial hematocrit+0.01)]. ABRI ⩾0.75 denotes failure. However, timing for hematocrit measurements was not defined. The aims of this study were: (1) to assess the Baveno IV criteria performance to classify treatment success or failure to control bleeding at 5days, (2) to determine the appropriate timing for hematocrit. Methods: Two hundred and forty-two cirrhotic patients with gastrointestinal bleeding were independently classified by three clinical experts according to the Baveno IV criteria, by analysis of the database of a randomized trial. ABRI was calculated by using the closest hematocrit to the 5day time point from the first trial product administration (ABRI-1) or after the latest transfusion within the 5-day period (ABRI-2). The gold standard for success/failure for 5-day control of bleeding was the clinical judgment of the three independent observers based on all the clinical and follow-up data. Results: Inter-observer agreement for the final outcome assessment was 0.82 and a final consensus was obtained in 236/242 patients. Inter-observer agreement on patient classification with Baveno IV criteria was 0.70 with ABRI-1 and 0.84 with ABRI-2. c-statistics for correct patients classification were 0.86 for ABRI-1, 0.84 for ABRI-2, and 0.88 for Baveno IV criteria without ABRI. ABRI-1 caused misclassification of 27 patients and ABRI-2 of 39. Conclusions: Baveno IV criteria are accurate to assess outcome of patients with variceal bleeding. There is a substantial observer variability linked to timing of hematocrits for ABRI calculation. With the current definition ABRI does not add to the performance of the other criteria. [ABSTRACT FROM AUTHOR]

These recommendations on video capsule endoscopy, an emerging technology with an impact on the practice of endoscopy, were developed by the European Society of Gastrointestinal Endoscopy (ESGE) Guidelines Committee. The first draft of each section was prepared by one or two members of the writing team, who were selected as experts on the content of that section on the basis of their published work. They used evidence-based methodology, performing MEDLINE and PubMed literature searches to identify relevant clinical studies. Abstracts from scientific meetings were included only if there was no published full paper on a particular topic. If there was disagreement, the first author of the Guideline made the final decision. Recommendations were graded according to the strength of the supporting evidence () . The draft guideline was critically reviewed by all authors and submitted to the ESGE councillors for their critical review before approval of the final document. The ESGE Guidelines Committee acknowledges that this document is based on a critical review of the data available at the time of preparation and that further studies may be needed to clarify some aspects. Moreover, this Guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This document should be regarded as supplying recommendations only to gastroenterologists in providing care to their patients. It is not a set of rules and should not be construed as establishing a legal standard of care, or as encouraging, advocating, requiring, or discouraging any particular treatment. These recommendations must be interpreted according to the clinician’s knowledge, expertise, and clinical judgment in the management of individual patients and, if necessary, a course of action that varies from recommendations must be undertaken. [ABSTRACT FROM AUTHOR]

Background Efficacy of heparin and low-molecular-weight heparins (LMWHs) in inflammatory bowel disease (IBD) treatment has been suggested. The multimatrix oral formulation MMX releases active drugs in the colon, avoiding systemic absorption. Parnaparin sodium is the LMWH chosen to be carried in the MMX formulation. Aim To assess the safety of three different oral dosages (70, 140 and 210 mg once daily) of Parnaparin-MMX (CB-01-05) in left-sided ulcerative colitis (UC). Methods Left-sided UC patients, with a mild-to-moderate relapse were enrolled. All patients received Parnaparin-MMX for 8 weeks. Clinical Activity Index (CAI), Disease Activity Index (DAI), Endoscopic Activity Index and IBD-QoL were assessed throughout the study. A strict clinical and laboratory follow-up, including assessment of anti-factor Xa activity, was performed. Clinical remission was defined as CAI <4. Results Ten UC patients were enrolled. One patient retired for clinical deterioration. No relevant side effects, including either interference with haemostasis parameters or increased bleeding, were observed. At the end of the treatment, seven patients (70%) were in clinical remission, only one achieving endoscopic healing. Mean final CAI, DAI and IBD-QoL scores were significantly improved from baseline. Conclusions Parnaparin-MMX appears to be a safe treatment option in mild-to-moderate UC. Controlled studies are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Hypofibrinolysis has been proposed as a possible mechanism underlying the known risk of thrombosis observed in patients with inflammatory bowel diseases (IBD). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. Increased TAFI plasma levels are associated with a risk for venous thrombosis. The objective was to evaluate TAFI plasma levels and their possible correlations with clinical features and acute-phase reactants in IBD patients.METHODS: Eighty-one IBD patients (47 Crohn's disease and 34 ulcerative colitis) and 81 sex- and age-matched healthy controls were enrolled in the study; moreover, we studied 30 inflammatory controls (13 Reiter's syndrome, 4 Behçet's syndrome, and 13 patients with newly diagnosed celiac disease). TAFI plasma levels were assessed by means of a commercially available ELISA kit. Erythrocytes sedimentation rate, C-reactive protein, andα1-acid glycoprotein were measured as acute-phase reactants. Statistical analysis was performed by means of nonparametric tests and Fisher's exact test andχ2 test for independence.RESULTS: Median TAFI plasma levels were significantly higher in IBD patients (116.0%, range: 39.0–232.0%) and in inflammatory controls (176.0%, 50.0–435.0%) than in healthy controls (99.0%, 40.0–170.0%) (p≤ 0.05 andp≤ 0.001, respectively). TAFI plasma levels higher than the 95th percentile of control values were significantly more frequent in IBD patients (19.7%) and in inflammatory controls (53.3%) than in healthy controls (4.9%) (p≤ 0.008 andp≤ 0.0001, respectively) and more frequent in clinically active IBD than in clinically quiescent IBD (31.4%vs10.9%,p≤ 0.03). Finally, in IBD, significant correlations were observed between TAFI plasma levels and erythrocytes sedimentation rate (p≤ 0.02), C-reactive protein (p≤ 0.001), andα1-acid glycoprotein (p≤ 0.05).CONCLUSIONS: TAFI plasma levels are increased in IBD patients and correlate with acute-phase reactants. Increased TAFI plasma levels might contribute to the prothrombotic state observed in IBD through the induction of hypofibrinolysis.(Am J Gastroenterol 2004;99:1966-1970) [ABSTRACT FROM AUTHOR]

Summary The diagnostic work-up of ulcerative colitis at presentation is based on the collection of clinical, microbiological, radiological, endoscopic and histologic data. Serological markers are characterized by too low a sensitivity to be commonly utilized in clinical practice. Although endoscopic and histologic features are characterized by very high sensitivity and specificity for the diagnosis of ulcerative colitis, negative stool cultures and parasites are mandatory to exclude an infectious aetiology at presentation. The treatment of choice of an acute flare-up of distal ulcerative colitis is represented by oral or topical mesalazine, or a combination of both, whereas the use of topical or systemic steroids should be restricted to patients who prove to be refractory to first-line treatments. Preliminary data suggest that the achievement of endoscopic and histologic remission after an acute flare of the disease might be associated with a prolonged remission. [ABSTRACT FROM AUTHOR]

Background: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. Aim: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. Methods: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4–12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. Results: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. Conclusions: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. Methods: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. Results: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. Conclusions: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) have been regarded as a possible immunogenetic marker of ulcerative colitis. If this were true, the p-ANCA status of a given patient should be constant over time; however, little information is available on this issue. Methods: One hundred and forty-five sera collected from 40 ulcerative colitis patients during a mean follow-up period of 50.6 months were tested for p-ANCA reactivity by indirect immunofluorescence. Results: At base line 24 patients (60%) were p-ANCA-positive, with no relationship to gender distribution, age at diagnosis, disease activity, or extension. During follow-up, changes in p-ANCA status occurred in 10 patients (25%). P-ANCA positivity during follow-up was associated with more aggressive forms of disease, whereas p-ANCA negativity was associated with stable remission. Conclusions: Changes in the p-ANCA status over time occur in some ulcerative colitis patients. P-ANCA behaviour is associated with different clinical patterns of disease. [ABSTRACT FROM AUTHOR]

Objective: To assess the long-term outcome in hepatitis B surface antigen (HBsAg) carriers who have normal liver function tests, focusing on survival and the development of severe liver disease and hepatocellular carcinoma.Design: Cohort study with a mean follow-up of 130 months.Setting: Liver clinic of a referral center.Patients: Ninety-two HBsAg-positive blood donors with normal liver function tests.Measurements: Histologic evaluation of liver specimens at baseline; clinical, biochemical, and serologic follow-up; and repeat liver biopsy if clinically indicated or after 10 years of follow-up.Results: At baseline, 69 subjects had normal histologic findings or only minor abnormalities, 18 had chronic persistent hepatitis, and 5 had mild chronic active hepatitis. Serum enzyme levels remained normal in 58 of 68 patients who had regular follow-up. Three patients had biochemical changes consistent with hepatitis B virus (HBV) infection; in one of these patients, a later histologic evaluation showed progression to chronic active hepatitis. One patient developed alcoholic cirrhosis. Six other patients had mild or transient transaminase elevations, with no evidence of HBV replication, hepatitis D virus infection, hepatitis C virus (HCV) infection, or histologic deterioration. Liver histologic findings also remained unchanged in 21 patients who showed no biochemical changes during 10 years of follow-up and consented to have repeated liver biopsy. Ten patients showed loss of HBsAg; 2 of these patients acquired antibody to hepatitis B surface antigen (anti-HBs). All patients who did not have regular follow-up, except 1, were interviewed by telephone during 1990: All denied having liver disease. No patients developed hepatocellular carcinoma.Conclusions: Italian HBsAg carriers with initially normal liver function tests have an excellent prognosis: Delta superinfection is infrequent and the risk for developing hepatocellular carcinoma is low. [ABSTRACT FROM AUTHOR]

Jejunal biopsies from patients with either dermatitis herpetiformis or cocliac disease were freeze-fractured and compared with normal jejunal biopsies. The intestinal mucosa of the normal biopsies showed a normal structure, with well-developed and tightly packed microvilli; in dermatitis herpetiformis and cocliac disease degenerative changes of the intestrial mucosa occurred. These changes appeared to he segmental in dermatitis herpetiformis and diffuse in coeliac disease. Emphasis is placed on changes in the tight junctional net at the base of the microvilli, which could represent cellular damage related to increased intestinal permeability to macromolecules in these diseases. An interpretative hypothesis for these observations is presented. [ABSTRACT FROM AUTHOR]