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Mesalazine enemas are of well proven efficacy for the topical treatment of distal ulcerative colitis. Although new rectal formulations of mesalazine are not expected to be superior in efficacy and tolerability to standard formulations, they may offer secondary advantages in terms of overall acceptability.To compare the efficacy, tolerability and overall acceptability of a new mesalazine rectal foam (Salofalk foam) with mesalazine enema in the treatment of active distal ulcerative colitis.A multicentre study was carried out in patients with active proctitis, proctosigmoiditis and left-sided ulcerative colitis as evaluated by the Clinical Activity Index (CAIor =4) and Endoscopic Index (EIor =6). Patients were randomly assigned to receive, in open-label fashion, either mesalazine foam 2 g twice a day or mesalazine enema (2 g/60 ml twice a day) for 3 weeks. Patients who did not achieve remission (defined as CAI4 and EI6) after 3 weeks continued the study receiving the alternative galenic formulation for a further 3 weeks.A total of 195 patients were enrolled. Characteristics at baseline were similar except for concomitant therapy with oral 5-ASA products: during the 1st treatment phase, 41% of patients on enema received such treatment vs only 29% of those on foam. Patients with at least one post-treatment efficacy evaluation were included in the intent-to-treat analysis (n=89 foam, n=96 enema). After 3 weeks of treatment, 112 patients were in remission and only 59 patients entered the 2nd treatment phase thus providing data on acceptability. Remission was achieved after 3 weeks in 54% of patients treated with foam and in 67% of those treated with enema. The 90% confidence interval for the difference in remission rates was 0 to 24 and thus within the clinically acceptable range of therapeutic equivalence. At the end of the 2nd phase, 70% of patients switched to foam were in remission vs 65% to the enema. Two patients discontinued treatment with foam prematurely due to anal burning. No clinically important changes were seen in the laboratory tests.Salofalk foam and enema are equally effective for the treatment of proctitis, proctosigmoiditis and left-sided ulcerative colitis. The new foam preparation is as well tolerated and accepted as enemas and can be used as a therapeutic alternative to conventional mesalazine enema formulations.

Background & Aims: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis with ascites. The International Ascites Club recommended strict diagnostic criteria and treatment with vasoconstrictors and albumin. Aim of this prospective cohort study was to investigate the prevalence of HRS, diagnostic criteria, treatment and 3-month outcome in the daily-clinical-practice. Methods: Two-hundred-fifty-three patients with cirrhosis and renal failure consecutively admitted to 21 Italian hospitals were recruited. Results: The prevalence of HRS was 45.8% (30% type-1 and 15.8% type-2). In 36% of cases HRS was presumed because not all diagnostic criteria could be fulfilled. In 8% of cases HRS was superimposed on an organic nephropathy. Patients with HRS type-1 were younger and showed higher leukocyte count, higher respiratory rates, and worse liver function scores. Sixty-four patients with HRS type-1 received vasoconstrictors (40 terlipressin and 24 midodrine/octreotide). A complete response was obtained in 19 cases (30%) and a partial response in 13 (20%). Age was the only independent predictor of response (p = 0.033). Three-month survival of patients with HRS type-1 was 19.7%. Survival was better in patients who responded to therapy. Age (p = 0.017), bilirubin (p = 0.012), and creatinine increase after diagnostic volume expansion (p = 0.02) independently predicted death. The mortality rate was 97% among patients with at least two negative predictors. Conclusions: The diagnostic criteria of HRS in our daily-clinical-practice could not be completely fulfilled in one third of cases. The treatment with vasoconstrictors and albumin was widely implemented. Mortality was strongly predicted by simple baseline variables.

Objectives: Efficacy of symbiotics in patients with irritable bowel syndrome (IBS) remains unknown. Methods: Patients were randomized to a prebiotic (n = 135), or a symbiotic formulation containing Lactobacillus paracasei B21060 (Flortec, n = 132). Primary efficacy was the responder rate for pain and global relief of symptoms in the overall population and in patients with predominant diarrhea (n = 47). Post hoc time-trend analyses for changes within each treatment were carried out. Results: Patients with absent/mild pain amounted to 54.7% in the symbiotic group and to 57.4% in the prebiotic group at treatment week 4, and to 53.9% and 53.4% at the end of treatment. Patients with amelioration of well-being were, respectively, 60.7% versus 61.7% at treatment week 4, and 63.3% versus 60.9% at the end of treatment. Within each treatment group, patients with absent/mild pain increased in the Flortec and the prebiotic group, but time trend analyses were significant only for Flortec (P = 0.019). In IBS-predominant diarrhea, Flortec significantly reduced bowel movements, pain, and IBS scores. Conclusions: To improve pain and well-being, Flortec is encouraging in patients with diarrhea predominant IBS. To establish its efficacy for the majority of IBS patients, Flortec has to be compared with an inert placebo in future work.

Background/Aims: Liver biopsy represents the gold standard to establish a diagnosis in all liver patients, but its current position in chronic viral hepatitis is questioned. We aimed to create a consensus on best practice of use of liver biopsy in the management of chronic HCV infection. Methods: We applied the Delphi method to 12 clinical scenarios of chronic HCV infection, to assess the extent of agreement (consensus measurement) and to resolve disagreement (consensus development) on the appropriateness of liver biopsy. Results: Among 108 chosen hepatologists, 61 (56.5%) accepted to participate to the first-round survey. In four patients the majority of experts (from 61.4 to 86.2%) agreed not to perform liver biopsy; in two cases an equivalent opinion was found, and in the remaining six scenarios the majority of experts would have recommended a biopsy. No expert recommended liver biopsy in all cases, while most agreed for an histological evaluation of 4 to 8 cases. At the second round, 36 experts (59%) submitted ballots. Fifty-four out of 431 (12.6%) original judgments were changed with equal distribution among different scenarios. Conclusions: Our survey showed a great divergence of management of similar patients and should provide a stimulus for an evidence-based evaluation of liver histology in chronic HCV infection. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Gene promoter methylation causes loss of tumor suppressor genes function in human cancer. Here, we show that the CDH4 gene, a member of the cadherin family encoding for R-cadherin, contains a CpG island located at the 5′ of the first exon, which functions as a promoter element and is frequently affected by methylation in human cancer. By using methylation-specific PCR and reverse transcription-PCR in human cancer cell lines, promoter methylation could be directly linked to loss of gene expression. After treatment with the demethylating agent 5-aza-2-deoxycytidine, expression could be restored. Analysis of human primary tumors revealed that the CDH4 gene is methylated in 78% (38 of 49) of colorectal and 95% (20 of 21) of gastric carcinomas. CDH4 methylation was not detected in nonneoplastic colonic (0 of 10) and stomach (0 of 10) tissues or in peripheral blood (0 of 17). CDH4 methylation was detected in histologically normal tissues located in proximity of the neoplasms, indicating that CDH4 methylation is an early event in gastrointestinal tumor progression. We also proved that CDH4 methylation can be revealed in the peripheral blood of cancer patients. Our results indicate that CDH4 may act as a tumor suppressor gene in human gastrointestinal tumors and can potentially be used as an early diagnostic marker for gastrointestinal tumorigenesis.