Angelo Pera

Effect of an Enteric-Coated Fish-Oil Preparation on Relapses in Crohn's Disease

BACKGROUND Patients with Crohns disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects. METHODS We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohns disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes. RESULTS Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7). CONCLUSIONS In patients with Crohns disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease

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

Predictive Factors of Mortality From Nonvariceal Upper Gastrointestinal Hemorrhage: A Multicenter Study

OBJECTIVES:From an Italian Registry of patients with upper gastrointestinal hemorrhage (UGIH), we assessed the clinical outcomes and explored the roles of clinical, endoscopic, and therapeutic factors on 30-day mortality in a real life setting.METHODS:Prospective analysis of consecutive patients endoscoped for UGIH at 23 community and tertiary care institutions from 2003 to 2004. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression analysis identified predictors of mortality.RESULTS:One thousand and twenty patients were included. A total of 46 patients died for an overall 4.5% mortality rate. In all, 85% of deaths were associated with one or more major comorbidity. Sixteen of 46 patients (35%) died within the first 24 h of the onset of bleeding. Of these, eight had been categorized as ASA class 1 or 2 and none of them was operated upon, despite a failure of endoscopic intention to treatment in four. Regression analysis showed advanced age, presence of severe comorbidity, low hemoglobin levels at presentation, and worsening health status as the only independent predictors of 30-day mortality (P < 0.001). The acute use of a PPI exerted a protective effect (OR 0.23, 95% CI 0.09–0.73). Recurrent bleeding was low (3.2%). Rebleeders accounted for only 11% of the total patients deceased (OR 3.27, 95% CI 1.5–11.2).CONCLUSIONS:These results indicate that 30-day mortality for nonvariceal bleeding is low. Deaths occurred predominantly in elderly patients with severe comorbidities or those with failure of endoscopic intention to treatment.

Infliximab and the risk of latent viruses reactivation in active Crohn's disease

Background: Infliximab is used for refractory Crohns disease but there are concerns regarding long‐term safety. Recently, JC‐polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short‐term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein–Barr virus (EBV), human herpes virus‐6, (HHV‐6), ‐7, ‐8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV‐positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV‐PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV‐6, ‐7, and ‐8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV‐PCR‐positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short‐term infliximab treatment with respect to latent virus reactivation. The long‐term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007)

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis : a multicenter comparative trial with 5-ASA enema

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P<0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI −7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living. The results of this study suggest that 5-ASA foam may provide prompter remission of symptoms compared to liquid enema and it improves the quality of topical therapy in ulcerative colitis.

Pregnancy before and after the diagnosis of inflammatory bowel diseases: Retrospective case–control study

Background and Aim:  Inflammatory bowel diseases (IBD) commonly affect women during the reproductive years. The aim of the present study was to evaluate the reproductive histories of patients with ulcerative colitis (UC) and Crohns disease (CD) considering pregnancies occurring before and after the diagnosis.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial

Objectives: A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. Methods: From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (≤ 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. Results: The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0–21) in the mesalazine b.i.d. group, 32% (95% CI: 16–49) in the mesalazine u.i.d. group, and 47% (95% CI: 29–65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. Conclusions: The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.

Controlled trial of oral 5‐aminosalicylic acid for the prevention of early relapse in Crohn's disease

Recent data indicate that 5‐aminosalicylic acid (5‐ASA) is most effective in preventing relapse of Crohns disease in patients with a short duration of remission before enrolment.

Abdominal pain and bowel dysfunction : diagnostic role of intestinal ultrasound

Background Abdominal pain and irregular bowel habits are common among young people. Irritable bowel syndrome is frequent in the general population and has important economic and social costs. Inflammatory bowel diseases are chronic processes with an acute or indolent onset in young people. Differential clinical diagnosis between irritable bowel syndrome and inflammatory bowel disease can be difficult since symptoms and signs are often non-specific. Objective To evaluate the role of intestinal ultrasound, a non-invasive, simple and cheap diagnostic tool, in the differentiation between organic and functional bowel diseases. Methods Abdominal and intestinal ultrasound examinations were performed on 313 consecutive outpatients presenting with abdominal pain and irregular bowel habits lasting more than 3 months. These patients had no symptoms or signs indicative of organic disorders and no previous diagnosis of organic disease. An intestinal wall thickness of more than 7 mm was considered diagnostic for inflammatory bowel disease. Subsequently, we compared the ultrasound results with diagnoses obtained following the traditional criteria (radiological and endoscopic examinations). Results Intestinal ultrasound for the diagnosis of inflammatory bowel disease showed 74% sensitivity, 98% specificity, a positive predictive value of 92% and a negative predictive value of 92%. Conclusions In our experience, intestinal ultrasound seems important as a first diagnostic tool in young patients without clear symptoms or signs of organic diseases, and can be used as an indication that subsequent invasive tests are required.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.

Objectives:A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis.Methods:From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (≤ 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features.Results:The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0–21) in the mesalazine b.i.d. group, 32% (95% CI: 16–49) in the mesalazine u.i.d. group, and 47% (95% CI: 29–65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p= 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up.Conclusions:The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.