Search

Endocrine-disrupting chemicals (EDCs) include widespread naturally occurring and synthetic substances in the environment that adversely affect humans and wildlife. Because of the increasing numbers of EDCs, screening methods and ideal biomarkers to determine EDC potencies at relevant environmental concentrations need to be drastically improved. Soluble guanylyl cyclase α1 subunit (sGCα1) is an abundant cytosolic protein ubiquitously expressed in most tissues. We previously showed that sGCα1 is specifically and highly up-regulated by estrogen (E2) in vivo and in vitro, even though it lacks estrogen-responsive elements. The aim of the present study was to evaluate sGCα1 protein expression as a potential marker for xenoestrogenic EDC exposure in the E2-responsive lactosomatotroph-derived pituitary cell line GH3. Cells were incubated with a wide variety of EDCs such as heavy metals and a metalloid, synthetic E2 derivatives, plastic byproducts, and pesticides at a range of doses including those with proven xenoestrogenic activity. We demonstrated that E2 increased sGCα1 expression in GH3 cells as well as in other E2-responsive tumor cell lines. Moreover, this effect was fully dependent on estrogen receptor (ER) activation. Importantly, sGCα1 protein levels were strongly up-regulated by all the EDCs tested, even by those exhibiting low or null ER binding capacity. We provide evidence that the in vitro sGCα1 protein assay may be a very sensitive and powerful tool to identify compounds with estrogenic activity, which could improve current mammalian-based screening methods. Environ Toxicol Chem 2019;38:2719-2728. © 2019 SETAC., (© 2019 SETAC.)

The aim of this study was to assess the genotoxic potential of surface waters located in a rural area in the north east of Buenos Aires province (Argentina) using the Allium cepa test. Water samples were collected at four sites located in a drainage channel and two sites on the Burgos stream that receives water from the channel, taking into account the sowing and harvesting months and rainfall periods. Analytical determinations revealed high total concentrations of Cd, Cu, Pb, and Zn (maximum values: 0.030, 0.252, 0.176, and 0.960 mg L -1 , respectively), and concentrations of glyphosate and its metabolite aminomethylphosphonic acid (AMPA), with maximum values of 13.6 and 9.75 μg L -1 , respectively. Statistically positive correlations were observed between the total metal concentrations and precipitation. No cytotoxicity (mitotic index MI) was observed in A. cepa. However, several water samples showed significant increases in micronucleus (MN) frequencies with respect to the controls. No correlations were observed between MN and the abiotic variables or precipitation. These results showed a state of deterioration in the water quality at the rural area studied in Buenos Aires province, and heavy metal contamination may contribute to the genotoxic activity. A. cepa was shown to be a useful tool for the detection of genotoxicity in water samples from areas with agricultural and livestock activities.

Background: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown., Aim: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients., Methods: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen., Results: The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class., Conclusion: This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC., (© 2018 John Wiley & Sons Ltd.)

Background: The expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs., Methods: The study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20 + 19 + 3 - 27 - 43 + ), memory B cells (MBs: CD20 + 19 + 3 - 27 + 43 - ), pre-plasmablasts (PPBs: CD20 + 19 + 3 - 27 + 43 + ), and plasmablasts (PBs: CD20 - 19 + 3 - 27 + 43 + )., Results: The total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p<0.001), and half that in the healthy controls (p=0.03). The between-group differences (including the healthy donors) were statistically significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only one treated patient showed a transiently large increase in PPBs. There were statistically significant differences in all of the parameters between the untreated patients and those receiving biological therapy, and in some cases between the untreated patients and healthy controls, but never between the controls and the treated patients. Four non-responders to anti-TNF therapy had a smaller number of total circulating B cells than the untreated patients., Conclusions: Anti-TNF drugs disinhibit B cell production in IBD patients, but maintain the constant homeostasis of circulating B cells. The presence of individual variations may allow the activity of anti-TNF drugs to be monitored by studying B cell subgroups., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/μL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile., (© 2014 John Wiley & Sons Ltd.)

Background: We have recently investigated the localisation of immunoglobulin-producing cells (IPCs) in inflamed intestinal tissue samples from patients with inflammatory bowel disease (IBD), and identified two main patterns of B lymphocyte infiltration: one characterised by the moderate strong stromal localisation of small B1 cell-like IgM+/CD79+/CD20-/CD21-/CD23-/CD5 ± IPCs, and the other by the peri-glandular localisation of IPCs with irregular nuclei that had surface markers specific for a B cell subset (IgM and CD79), but quantitative differences in their λ and κ chains. The same patients were also tested for CD15+ receptors, which were localised on inflammatory cell surfaces or in the crypts of the intestinal epithelium. CD15+ receptor distribution in inflamed tissues was limited to the cell structures. The aim of the study was to analyse variations in IPCs and CD15+ cell morphology or distribution in bowel biopsy specimens taken from patients with pre-malignant polyps or adenocarcinomas., Methods: IPCs were analysed by means of immunofluorescence using polyclonal goat anti-human μ chains. The pre-malignant polyp specimens were tested for B cell surface phenotype λ and κ chains, CD79, CD20, CD21 and CD23 using an immunoperoxidase method. CD15+ cells were evaluated using the immunoperoxidase method and monoclonal anti-CD15 IgM., Results: The study involved 14 patients (four with pre-malignant polyps and 10 with colorectal adenocarcinomas). The distribution of μ chains and CD15 markers varied in all of the biopsies, but delineated normal cell structures in the pre-malignant polyp specimens. B cell surface phenotype analysis of μ chain-positive cells identified a subset of CD79+/CD20-/CD21-/CD23- IPCs. The IPCs in certain areas showed the sporadic disintegration of inflammatory cell membranes or the accumulation of fluorescence in individual cells. IPC membrane disintegration was particularly marked in all of the adenocarcinoma samples, in which the CD15 markers also showed epithelial cell involvement. Furthermore, six of the ten adenocarcinoma samples had atypical and reorganised membranes that expressed an excess of both receptors and isolated small portions of tissue within the tumour., Conclusion: The findings of this preliminary morphological study suggest the presence of membrane disintegration and remodelling mechanisms in the tumours. The newly-formed membranes expressed high concentrations of inflammatory cell receptors that can confer adhesive properties.

B lymphocytes express various different types of surface immunoglobulins that are largely unrelated to other hematological lines, although some reports have described a relationship between malignant B cells and other cells such as macrophages. Multiple genes of hematopoietic lineage, including transcription factors, are co-expressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming". Changes in the expression levels and timing of transcription factors can induce the lineage conversion of committed cells, which indicates that the regulation of transcription factors might be particularly critical for maintaining hierarchical hematopoietic development. The aim of this study was to evaluate the surface markers of particular IgM-positive and irregularly nucleated cells detected in patients with inflammatory bowel disease (IBD), and to assess their association with diagnosis and inflammatory cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The specimens positive for B cells with irregular nuclei were assessed using monoclonal antibodies specific for CD79, and λ and κ chains in order to confirm their B cell nature. CD15+ cells, an important marker of inflammatory cell recruitment, were also evaluated. Statistical correlations were sought between the histological findings and clinical expression. 34 (35.4%) of the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease) presented a periglandial localization of IPCs with irregular nuclei, which showed surface markers specific for the B cell subset, such as IgM and CD79, but quantitative differences in λ and κ chains. These specimens also contained CD15-positive cells, which are usually absent in healthy controls. The quantitative aspects and localization of the CD15-positive cells correlated with the distribution of the IPCs with irregular nuclei. IPCs with irregular nuclei were significantly more frequent in those patients with Crohn's disease than in those with ulcerative colitis (p<0.001). The finding of a subpopulation of cells that simultaneously showed irregular nuclei and B cell markers, such as functional surface IgM, in patients with IBD suggests that an unusual subgroup of B cells that correlates with CD15 expression and a diagnosis of Crohn's disease may be observed in the inflammatory process., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Methotrexate is considered a treatment for Crohn's disease, whilst few data in ulcerative colitis are available., Aim: To evaluate frequency, indications, efficacy and safety of methotrexate in inflammatory bowel disease patients., Methods: 5420 case histories were reviewed., Results: Methotrexate was prescribed to 112 patients (2.1%; 89 Crohn's disease, 23 ulcerative colitis). It was the first-line immunosuppressive option in 32 (28.6%), it was an alternative drug due to toxicity or failure of thiopurines in 80 (71.4%). Steroid-dependence represented the main indication both when it was used as first (13/32, 40.6%) and second option (41/80, 51.2%). Efficacy was considered optimal in 39/112 (34.8%), partial in 29/112 (25.9%), absent in 22/112 (19.6%), not assessable in 22/112 (19.6%). Side effects happened in 49 out of 112 patients (43.7%) (39 Crohn's disease, 10 ulcerative colitis), leading to drug discontinuation in 38 (33.9%). The occurrence of side effects was approximately fivefold higher in patients who did not receive folic acid (14/19, 73.7%) than in those who did (35/93, 37.6%): odds ratio 4.64, 95% confidence interval 1.54-14.00; p=0.005., Conclusions: The use of methotrexate appears to be negligible in clinical practice. However, our results suggest that, if appropriately used, methotrexate could be more widely administered to inflammatory bowel disease patients with complicated disease., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is thought to be due to an abnormal interaction between the host immune system and commensal microflora. Within the intestinal immune system, B cells produce physiologically natural antibodies but pathologically atypical anti-neutrophil antibodies (xANCAs) are frequently observed in patients with IBD. The objective is to investigate the localisation of immunoglobulin-producing cells (IPCs) in samples of inflamed intestinal tissue taken from patients with IBD, and their possible relationship with clinical features., Methods: The IPCs in small intestinal, colonic and rectal biopsy specimens of patients with IBD were analysed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The B cell phenotype of the IPC-positive samples was assessed using monoclonal antibodies specific for CD79, CD20, CD23, CD21, CD5, λ and κ chains. Statistical correlations were sought between the histological findings and clinical expression., Results: The study involved 96 patients (64 with ulcerative colitis and 32 with Crohn's disease). Two different patterns of B lymphocyte infiltrates were found in the intestinal tissue: one was characterised by a strong to moderate stromal localisation of small IgM+/CD79+/CD20-/CD21-/CD23-/CD5± IPCs (42.7% of cases); in the other (57.3%) no such small IPCs were detected in stromal or epithelial tissues. IPCs were significantly less frequent in the patients with Crohn's disease than in those with ulcerative colitis (p = 0.004)., Conclusion: Our findings suggest that different immunopathogenetic pathways underlie chronic intestinal inflammation with different clinical expressions. The presence of small B lymphocytes resembling B-1 cells also seemed to be negatively associated with Crohn's disease. It can therefore be inferred that the gut contains an alternative population of B cells that have a regulatory function.

Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated., Aim: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically, Methods: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis., Results: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0%vs 58.7%, P= 0.03), had lower transaminase levels (3.3 +/- 2.0 vs 3.8 +/- 2.5 u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3%vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76-1.95)., Conclusions: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.

Background & Aims: Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone., Methods: In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored., Results: Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups., Conclusions: Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Background: Management of perianal and rectovaginal fistulae complicating Crohn's disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome., Methods: Thirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months., Results: Fifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract., Conclusions: Infliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.

Background and Aim: Ten years ago we published a study describing the 6-month outcome of 33 outpatients with typical gastro-oesophageal reflux disease symptoms and pH-metry proven excess gastro-oesophageal reflux but without endoscopical evidence of oesophagitis, currently referred to as patients with gastro-oesophageal reflux disease without oesophagitis. We now present an update of that report concerning morbidity, drug consumption and quality of life of the original patients 10 years after the initial diagnosis., Methods: The study consisted of the retrieval and revision of all clinical and instrumental records concerning the cohort of 33 above-mentioned patients. Data are available regarding annual intervals within the first 5 years from original diagnosis and, subsequently, with a follow-up ranging from 7 to 14 years (median 10 years). The records of these 33 patients were reviewed, including the results of clinical visits at the outpatients department, of oesophagogastroduodenoscopies and pH- metries. Finally, a telephonic interview was conducted by means of a structured questionnaire, aiming at evaluating present symptoms, actual therapy if any, health-related quality of life and other information regarding any gastro-oesophageal reflux disease symptoms., Results: Of the original 33 patients, 31 are still alive and 2 were lost to follow-up. Of the 29 remaining, only 1 is definitively not complaining of any gastro-oesophageal reflux disease-related symptoms. Within 5 years of the first diagnosis, oesophagitis was found in all but one of the 18 subjects who underwent repeated endoscopy. At the latest follow-up check, after a median of 10 years, out of the 28 still complaining of gastro-oesophageal reflux disease symptoms, 21 (75%) were presently taking antisecretory drugs (proton pump inhibitors and H-2 receptor antagonists) because of gastro-oesophageal reflux disease symptoms/lesions, 12 of whom intermittently or on demand and the remaining 9 continuously. Two patients (2/28) underwent antireflux surgery, but despite this were still taking antisecretory drugs (in one case H2-RA; in the other proton pump inhibitor). The health-related quality of life, self-evaluated by the patient by means of a VAS scoring from 0 (worst possible) to 10 (best possible) increased significantly from 3.2 to 6.5 from baseline (before therapy) to present time, possibly due to the positive effect of present therapy., Conclusions: Our study conducted on a cohort of endoscopy-negative patients with pH-metry-confirmed reflux disease has shown that after a median time of 10 years following the original diagnosis, the majority of patients have, in fact, developed reflux oesophagitis and are on prolonged antisecretory therapy because of recurrent gastro-oesophageal reflux disease symptoms/lesions. The study confirms that gastro-oesophageal reflux disease without oesophagitis, as well as gastro-oesophageal reflux disease at large, is a chronic disease characterised by increasing severity with time, which requires protracted medical therapy in a vast proportion of patients. Absence of endoscopic oesophagitis at presentation does not represent a positive prognostic factor.

Background: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an 'organic' disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a 'functional' disorder (i.e. illness thought to be more in the 'mind' than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health-related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study., Methods: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF-36 (a generic well-validated tool for measuring HRQOL), the SCL-90 (for assessing the psychological profile of patients), and the Holmes & Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni-adjusted t test, when appropriate., Results: HRQOL appeared to be similarly reduced in both disease groups (SF-36 overall mean value: 58.2 +/- 16.1 in IBS patients versus 56.4 +/- 22.3 in IBD patients: P > 0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL-90 mean scores of 0.89 + 0.45 versus 0.83 +/- 0.48, respectively (P > 0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8 = 110.2 versus 61.6 +/- 78.8; P < 0.05)., Conclusion: Our study supports the notion that, at least in referral centres, patients with IBS show health-related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age-matched IBD patients.

Background and Aims: The efficacy of azathioprine in the treatment of chronic active Crohn's disease is well established. However, this drug has a long onset of action. Methotrexate has also been shown to be effective in chronic active Crohn's disease. The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine, and to establish whether methotrexate has a shorter onset of action in this setting., Methods: Patients with chronic active Crohn's disease were admitted to this investigator-blind study. Chronicity was defined as the need for steroid therapy of > or = 10 mg/day for at least 4 months during the preceding 12 months, with at least one attempt to discontinue treatment. The disease had to be clinically active at entry, with a Crohn's Disease Activity Index of > or = 200. Six patients treated with azathioprine and methotrexate, respectively, were found to have enterocutaneous and perianal fistulas. At entry, all patients received prednisolone (40 mg once a day) which was tapered over a period of 12 weeks unless their clinical condition deteriorated. All patients were randomised to receive i.v. methotrexate 25 mg/week, or oral azathioprine 2 mg/kg per day, for a 6-month follow-up period. After the first 3 months, methotrexate was switched to oral administration maintaining the same dose. The primary efficacy outcome considered was the proportion of patients entering first remission after 3 and 6 months of therapy. Clinical remission was defined as the lack of need for steroid treatment and a Crohn's Disease Activity Index score of < or = 150 points at each scheduled visit., Results: In the 54 patients (26 F, 28 M, mean age 34 years, range 18-60) randomly assigned to methotrexate (n=27) or azathioprine (n=27), no statistically significant difference was found between the two treatment regimens with respect to remission rate after 3 (methotrexate 44%, azathioprine 33%, p=0.28, (95% CI, 0.369-0.147), and 6 months (methotrexate 56%, azathioprine 63%, p=0.39, 95% CI, 0.187-0.335), respectively. Six patients withdrew from therapy due to adverse events: 3/27 (11%) in methotrexate and 3/27 (11%) in azathioprine. Drug-related adverse events (asthenia, nausea and vomiting) that did not require withdrawal from therapy were more frequent in the methotrexate group (azathioprine: 2/27 (7%); methotrexate: 12/27 (44%), p=0.00009). The frequency of these adverse events was comparable during the intravenous or oral administration of the drug., Conclusions: This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohn's disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine.

Background: A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce., Methods: The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis., Results: Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009)., Conclusions: The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Background: Efficacy of infliximab in treatment of patients with moderate-to-severe refractory and fistulizing Crohn's disease has been shown in controlled clinical trials. Moreover, audit data from North America and North Europe have confirmed efficacy in clinical practice comparable to that in clinical trials., Aim: To report clinical experience using infliximab in treatment of Crohn's disease in Italy, comparing efficacy and safety with those reported in clinical trials and other published series., Patients and Methods: The study population comprised 63 patients (31 males and 32 females, median age 33 years) treated with infliximab for refractory/inflammatory (31 patients) and/or fistulizing Crohn's disease (32 patients). All patients received an infusion of infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6. After the first infusion, clinical and laboratory assessments were repeated at weeks 2, 6 and 10. For refractory inflammatory Crohn's disease, clinical remission was defined as a Crohn's Disease Activity Index of < or = 150 at each scheduled visit, clinical response as a reduction in the Crohn's Disease Activity Index score of > or = 70 points in comparison to baseline. For fistulizing Crohn's disease, a complete response was defined as closure of any draining fistulae at week 10. A fistula was defined as closed when it no longer drained despite gentle finger pressure. A partial response was defined as reduction in number, size or drainage of fistulae, at the same visit., Results: According to an intention-to-treat evaluation on the 31 patients with refractory/inflammatory Crohn's disease, at week 2, 42.5% (14 patients) had a clinical response and 31.3% of patients (10 patients) were in clinical remission. At week 10 (4 weeks after the end of third infusion), 80.6% (25 patients) had a clinical response and 71% (22 patients) were in clinical remission and 14/19 (74%) had discontinued steroid treatment. Of the 32 patients with fistulizing Crohn's Disease, 15 (46.9%) had a complete response, 8 (25%) a partial response, and 9 (28.1%) no response at week 10 check-up. The incidence of side-effects was low (16%) and not influenced by concurrent immunomodulatory therapy., Conclusion: The present experience with infliximab in clinical practice confirms its efficacy, in particular in inflammatory/refractory Crohn's disease and its safety, at least, in short-term follow-up.

Aim: To evaluate the efficacy of power Doppler sonography (US) in depicting internal fistulae and their vascularity, and to study the characteristics of blood flow within the fistula wall., Patients and Methods: The study involved 45 consecutive patients with Crohn's disease and suspected internal fistulae detected by grey scale US. The fistulae were subsequently evaluated using power Doppler US to reveal any areas of increased vascularity, and the results were compared with radiographic, endoscopic, or intraoperative findings. Whenever feasible, we also performed spectral analysis of blood flow revealed by power Doppler US, calculated its resistance index (RI), and analysed its characteristics, reproducibility, and relationship with biochemical and clinical variables (Crohn's disease activity index, disease duration, location, and abdominal complications)., Results: Power Doppler US revealed vascularity in all of the internal fistulae that where subsequently confirmed by diagnostic procedures. In the case of intra-abdominal abscesses in the vicinity of the fistula, vascular signals were detected mostly around and not within the lesions. The intensity and distribution of the signals differed within the fistulae tracks and had only slight day to day reproducibility; furthermore, there was no significant correlation with clinical or biochemical variables. Spectral analyses of blood flow within the fistulae revealed arterial flow in 96.7% of patients (median RI 0.715). RI was a more reproducible parameter and significantly correlated with clinical (r= 0.54) and biochemical activity (r= 0.56) of CD. It was also higher in fistulae complicated by abscesses., Conclusion: Power Doppler US can reveal the presence of vasculature within the wall of internal fistulae and therefore enhance grey scale US performance. The RI characteristics of blood flow within the fistulae are reproducible and correlate with biochemical and clinical disease activity.

Background and Aim: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohn's disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with x ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel., Methods: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel x ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with x ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD)., Results: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by x ray (r=0.52, p<0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (r=0.64, p<0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively., Conclusions: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription., (Copyright 2001 S. Karger AG, Basel)

Background: Conservative surgery has become accepted as a useful option for the surgical treatment of complicated Crohn's disease (CD)., Methods: One hundred thirty-eight consecutive patients treated with strictureplasty or miniresections for complicated CD have been observed prospectively. The possible influence of a number of variables on the risk of recurrence was investigated using the Cox proportional hazard model, and a time-to-event analysis was made using the Kaplan-Meier function., Results: There was no perioperative mortality; the morbidity rate was 5.7%. A close correlation was found between the risk of recurrence and the time between diagnosis and first surgery. The overall 5-year recurrence rate was 24%, being 36% in the patients requiring surgery within 1 year of diagnosis and 14% in those operated on more than 1 year after diagnosis., Conclusions: Risk factor analysis highlighted a group of patients at high risk of surgical recurrence. Given that our results are similar to those reported in other series, we consider strictureplasty and miniresections safe and effective procedures for the treatment of complicated CD.

Objectives: To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants., Methods: We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis., Results: Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features., Conclusions: Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.

Objectives: The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases., Design and Setting: This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992-95 in one research clinic in Milan., Subjects and Methods: Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 +/- 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. +/- 12.5 years) entered the study. Thirty healthy subjects were selected as sex- and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D3; 1,25-hydroxycholecalciferol, 1, 25(OH)D3) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen C-terminal telopeptide, ICTP) were evaluated., Results: Spine and femur T scores were similar in the two groups (spine: CD = -1.49 +/- 1.46; UC = -1. 67 +/- 1.13; femur: CD = -1.80 +/- 1.36; UC = -1.60 +/- 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D3 concentrations were significantly lower in both CD and UC patients compared with controls (P < 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 +/- 5.06, UC = 10.03 +/- 6.24, C = 6. 58 +/- 2.87, P < 0.05 vs. C) and ICTP (CD = 5.74 +/- 3.94, UC = 10.2 +/- 8.47, C = 3.48 +/- 0.95, P < 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r2 = 0.107, F = 5.49) and significantly related to sex (more negative in males: r2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r2 = 0.283, F = 7.3)., Conclusions: These data show that IBD patients have a diffuse osteopenia, the degree of which is not different in CD and UC; however, bone turnover is significantly higher in UC. Finally, osteopenia is related to disease duration in CD, whilst it is related to the male sex and glucocorticoid treatment in UC.

Background: The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence., Aim: To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission., Methods: 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year., Results: We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A., Conclusions: Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.

The aetiology of inflammatory bowel disease remains unknown, but genetic, immuno-inflammatory, infectious, vascular and neural factors play an important role. All effective treatments in use today were introduced empirically and most have multiple action. Targeted therapy is very attractive, either with cell and gene therapy or by using specific cytokine inhibitors and inhibitory cytokines. The role of the intestinal milieu, and enteric flora in particular, appears to have a much greater significance than previously appreciated. The reduction of any changes leading to pro-coagulant activity may be a promising line of therapeutic investigation, and measures to reduce platelet aggregation and endothelial cell adhesiveness are examples of therapeutic potentials. Finally, there has been tangible demonstration of the ability of nerves to alter the inflammatory process which will lead to new therapeutic approaches in inflammatory bowel disease.

Background: Current knowledge on splanchnic haemodynamics in Crohn's disease is limited., Aims: To investigate which features of Crohn's disease affect splanchnic haemodynamics, and to establish whether portal vein (PV) and superior mesenteric artery (SMA) blood supply reflects clinical or biochemical activity of Crohn's disease., Methods: Seventy nine patients with Crohn's disease and 40 controls were evaluated by Doppler ultrasound (US). The mean velocity of PV and SMA flow, the volume of blood flow of the PV and SMA, and the resistance index of SMA were studied. A series of clinical, biochemical, and US variables including Crohn's disease activity index, serum C reactive protein concentrations, disease duration and its anatomical location, smoking habits, abdominal complications, and current medical therapy, as well as the maximum bowel wall thickness as measured by US, were determined. The relation between PV and SMA blood flow and these variables was assessed by univariate and multivariate analysis., Results: Patients with Crohn's disease had significantly higher PV and SMA flow and a lower SMA resistance index than controls. Stepwise multiple regression analysis identified bowel wall thickness and location of the disease as the main predictive variables of both PV and SMA blood flow variation, accounting for 36% and 45% of their variability, respectively. No relation was found between splanchnic haemodynamics and disease activity., Conclusion: A hyperdynamic mesenteric circulation does exist in Crohn's disease; however splanchnic blood flow does not reflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn's disease characteristics, such as maximum bowel thickness and anatomical location.

Background: Data on the natural history of reflux oesophagitis are few and conflicting: it is not clear whether in the long-term, patients still require therapy for controlling symptoms and preventing endoscopic relapse., Aims: To assess, in reflux oesophagitis patients followed up for a median period of 4 years: a) clinical conditions throughout follow-up period (i.e., frequency of relapses, need and type of treatment, satisfaction with therapy; b) present state, including quality of life, mode of treatment, presence of residual symptoms or invalidity., Patients: A series of 288 consecutive outpatients, diagnosed as having reflux oesophagitis during the period 1986-1990, and followed up for at least 48 months., Methods: The study was carried out in two parts. The first, retrospective, assessing the outcome throughout follow-up during which it was suggested that patients assume a maintenance therapy with H2-receptor antagonists, proton pump inhibitors or other drugs for the first year, and to continue only if desired. Patients returned for follow-up every six months, and endoscopy was repeated after the first year or in the case of symptom recurrence. In the second part, after a median follow-up of 4 years, patients were submitted to a telephone interview by means of a structured questionnaire, assessing type and severity of current symptoms (if any), type of current therapy, degree of satisfaction with treatment, and overall evaluation of quality of life., Results: Data are available from 132 patients (M/F = 85/47) of whom 119 (90%) were still on treatment and 31% still presented symptoms. During follow-up, 21% had more than 3 endoscopic relapses, 23% between 2 and 3, 28% one, and 28% zero, respectively and 79% were still adopting non-pharmacological measures (diet, posture, etc.). Only two (1.5%) had been submitted to surgery to control untractable symptoms/mucosal lesions. Finally, 64% and 11%, respectively, considered the present quality of life as good or excellent., Conclusions: Contrary to many reports, the prognosis of reflux oesophagitis is not favourable showing a marked trend to chronicity; the disease leads to almost continuous drug assumption for symptom control, and is associated with a high relapse risk after treatment withdrawal. Despite (or due to) these unfavourable features, patient compliance to both pharmacological and non-pharmacological therapy is excellent and, correspondingly, also the quality of life is acceptable or improved.

Background/aims: Reduction of gastric acid secretion by maintenance treatment with antisecretory agents and eradication of H. pylori by antibiotics constitute the most effective therapeutic options in preventing duodenal ulcer relapse. The aim of this study was to compare the effect of a 12-month low-dose lansoprazole maintenance treatment with H. pylori eradication on the rate of ulcer relapse in H. pylori-positive duodenal ulcer patients., Methodology: After a healing phase with lansoprazole 30 mg/die or lansoprazole 30-60 mg/die plus antibiotics (amoxycillin, tinidazole and colloidal bismuth subcitrate), 84 patients with healed duodenal ulcer entered the follow-up phase. Thirty-eight patients with persistent H. pylori infection received lansoprazole 15 mg at bedtime, whereas 46 in whom H. pylori was eradicated during the acute phase received no active therapy during the 12-month follow-up. The two groups were well balanced concerning all demographic characteristics. Clinical controls were performed every 3 months or sooner in the event of symptomatic relapse., Results: In terms of per protocol analysis, the overall rate of ulcer relapse at 6 months was 5.5% (2/36) in the maintenance group and 0 (0/42) in the antibiotic group. The corresponding figures at 12 months were 20.5% (7/34) and 5.7% (2/35), respectively (p:ns, 95% CI for the difference -0.30+0.02). On intent to treat analysis, the rate of ulcer relapse at 6 months was 5.2% (2/38) in the first group and 0% (0/46) in the second group: at 12 months the corresponding figures were 19.4% (7/36) and 4.3% (2/46), respectively (p=0.06; CI 95%: +0.016+0.28). No significant side effects were observed during long-term maintenance with lansoprazole., Conclusions: Continuous maintenance with low-dose lansoprazole may constitute a valuable alternative to H. pylori eradication for the prevention of relapse and complications in duodenal ulcer patients not suitable for, or who have failed, H. pylori eradication.

Background: Although a reduced prevalence of Helicobacter pylori infection has been observed in inflammatory bowel disease (IBD) patients, the clinical significance of H. pylori infection in this setting remains unknown. The aim of this study was, therefore, to evaluate the prevalence of H. pylori infection in a large series of IBD patients and the frequency of gastroduodenal lesions in those who agreed to undergo upper GI endoscopy., Methods: Two hundred and sixteen consecutive IBD patients (123 with Crohn's disease (CD) and 93 with ulcerative colitis (UC)) had their anti-H. pylori IgG titres measured. Two hundred and sixteen blood donors matched for age, sex, place of birth in Italy, and socioeconomic status served as controls. All patients were offered the possibility of undergoing endoscopy with antral and corpus biopsies regardless of their H. pylori status., Results: The overall seroprevalence of H. pylori infection was 48% in IBD patients versus 59% in the control group (P < 0.05), with a significantly lower frequency in CD versus UC patients (41% versus 56%). After adjustment for age, education, and socioeconomic status CD remained associated with a significantly lower risk of H. pylori infection. Previous therapy with sulphasalazine but not with 5-aminosalicylic acid or with steroids/immunosuppressants was associated with a reduced risk of H. pylori infection both in CD and UC patients. One hundred and eighty-nine patients (110 with CD and 79 with UC) underwent endoscopy; the prevalence of peptic ulcer was similar in both groups (5.5% in CD and 5.1% in UC patients); however, 11 more CD patients had gastroduodenal ulcers that were interpreted as CD-related; 7 of these patients had never had foregut symptoms. Two CD patients had granulomatous gastritis at histology, and another 16 patients with CD had H. pylori-negative gastritis., Conclusions: IBD patients have a reduced prevalence of H. pylori infection as compared with matched healthy controls; this appears mostly attributable to a reduced frequency of H. pylori colonization in CD patients. Previous use of sulphasalazine is associated with a reduced risk of infection both in CD and UC patients. Of CD patients 10% have a gastroduodenal localization of their disease, which is often asymptomatic. Of CD patients 15% also have H. pylori-negative gastritis at histology.

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.

We evaluated, retrospectively, the outcome of 56 patients (39 male, 17 female; mean age, 34 years; age range, 14-65 years) who received azathioprine for either steroid-resistant (group A, n = 10) or steroid-dependent (group B, n = 46) ulcerative colitis. The patients were followed for a mean of 29 +/- 17 months (median, 27 months). Twenty-four had left-sided colitis, 5 had subtotal colitis, and 27 had total colitis. The mean duration of the disease was 51 months (range, 2-192 months). At the beginning of azathioprine treatment (time 0), all patients had clinically severe disease and were taking 40 mg prednisolone per day. Azathioprine was used in addition to steroid therapy at a dosage of 2 mg/kg. The need for steroids, expressed as the median cumulative steroid dose (mg/year), and the number of clinical relapses (requiring steroid therapy) in the 2 years before azathioprine treatment, were compared with those of the 3-year follow-up with azathioprine treatment. A positive response to azathioprine was defined as (a) avoidance of colectomy, (b) a significant decrease in the median cumulative steroid dose, and (c) a significant decrease in the number of clinical relapses (expressed as number/patient/year). One patient in group A withdrew due to painful dyspepsia, and two patients in group B were lost to follow-up. Remission with complete elimination of steroids was achieved in 36 of 53 (64%), 23 of 35 (66%), and 18 of 26 (69%) patients in the first, second, and third years, respectively, of azathioprine treatment. Compared with the 2 years before azathioprine treatment, a significant decrease was observed of about 75% both in steroid consumption and in the number of clinical relapses during the 3 years of azathioprine therapy. Two of nine patients in group A and 2 of 44 patients in group B had colectomy after mean periods of 15 months and 24 months, respectively. Azathioprine is effective and safe in avoiding colectomy in patients with steroid-resistant and steroid-dependent ulcerative colitis; its use decreases both steroid requirements and clinical relapses.

The aim of this study was to evaluate the sensitivity and specificity of ultrasound (US) in assessing the main abdominal complications of Crohn's disease (CD), such as strictures, fistulas and abscesses. A series of 98 consecutive inpatients with complicated and uncomplicated Crohn's disease, having undergone a complete endoscopic and radiographic evaluation of the intestinal tract, entered the study. In particular, in these patients the presence of strictures, fistulas, and abscesses, detected by means of colonoscopy, small bowel x-ray, double-contrast barium enema, and computed tomography, was also assessed by means of transabdominal US. US sensitivity and specificity in the assessment of stenosis of Crohn's disease were 74.4% and 93.1%, respectively. When ileal and colonic stenosis were considered separately, transabdominal US correctly assessed 84.6% of ileal stenosis and 58.8% of colonic stenosis. Eight of 12 fistulas were detected, but only 50% of enteroenteric fistulas were diagnosed. The presence of abscesses was correctly detected in 83.3% of cases by means of US. Our data suggest that US is a suitable complementary method for the detection of abdominal complications of Crohn's disease, such as strictures and abscesses; however, its usefulness in assessing enteroenteric fistulas seems to be fairly limited.

Aims: The aim of this study was to evaluate the relevance of ultrasound (US) in assessing disease extent and activity in a series of patients with quiescent or active Crohn's disease (CD). In particular, the study was aimed at evaluating whether US may be useful in distinguishing between active disease and bowel wall thickening (BWT) due to fibrosis., Patients and Methods: A series of consecutive patients with ileal, ileo-colonic, or colonic CD previously studied with x-ray and/or endoscopy, underwent abdominal US. The following parameters were also determined in these patients: CD activity index (CDAI), erythrocyte sedimentation rate, C reactive protein, length of disease, previous surgical resection, and number of recurrences. The relationship between BWT and the aforesaid parameters was assessed by means of univariate and multiple regression analysis., Results: Overall sensitivity and specificity of US for the assessment of anatomical distribution of CD were 89% and 94%, respectively, and there was also a significant correlation between the extent of ileal disease measured by US and that determined by small bowel x-ray. By univariate analysis, statistically significant correlations were found between BWT, CDAI, and biological indices of inflammation (erythrocyte sedimentation rate and C reactive protein), although all the correlation coefficients were low with values not exceeding 0.40, and among these, backward multiple regression analysis identified only CDAI, along with ileo-colonic localization, as the subset of predictive variables of bowel wall thickness. However, both predictions were rather weak and accounted for only 20% of the variability of the BWT. In addition, a significant relationship was found between disease US extent and clinical or biochemical disease activity. However, in a subgroup of patients characterized by quiescent disease and high BWT, CD was complicated by higher prevalence of strictures, as detected by radiological and endoscopic examinations, and more frequent surgical outcome than others., Conclusions: Abdominal US is an accurate method for determining the abdominal distribution of CD and appears to be accurate in detecting and evaluating the disease length of ileal lesions. In contrast, despite a weak but significant correlation between BWT and clinical and biochemical parameters, the usefulness of US as an index of disease activity seems to be fairly limited. However, a high BWT in quiescent patients suggests the presence of fibrosis, which is poorly responsive to steroid treatment.