Filippo Mocciaro

Meta-Analysis of the Placebo Rates of Clinical Relapse and Severe Endoscopic Recurrence in Postoperative Crohn's Disease

BACKGROUNDS & AIMS The benefit of therapy for prevention of postoperative recurrence of Crohns disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurrence in postoperative CD and to identify factors influencing these rates. METHODS We performed a meta-analysis of placebo-controlled, randomized clinical trials, evaluating therapies for postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe endoscopic recurrence. RESULTS The pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval [CI], 13-35; range 0-78). There was a statistically significant heterogeneity among studies (P < .0001). Heterogeneity in clinical relapse was present even if the trials were stratified according to the time of outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79). There was significant heterogeneity among the studies (P = .00038). This heterogeneity was less apparent in studies carried out within 12 months. The logistic analysis identified only duration of follow-up as a variable associated with different placebo relapse rates. No variable was identified as a predictor of a placebo endoscopic recurrence rate. CONCLUSIONS There is significant heterogeneity among placebo rates in postoperative CD. No single design variable was identified that explained the heterogeneity in placebo outcomes for clinical or endoscopic recurrence.

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures.

AIM To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohns disease strictures. METHODS Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohns disease patients with 39 intestinal symptomatic strictures (4 naïve and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan-Meier method. Demographic and disease variables were related to the main outcomes. RESULTS After a mean follow-up of 26.3 months (range, 2-61 months), the long-term global benefit rate was 89% (33/37). The 1-2-3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures. CONCLUSIONS Endoscopic balloon dilation of symptomatic Crohns disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: early and long-term data from a retrospective observational study.

INTRODUCTION About 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice. METHODS We reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up. RESULTS A total of 65 patients were included: 35 in the cyclosporine group and 30 in the infliximab one. At 3 months the colectomy rate was 28.5% in the cyclosporine group and 17% in the infliximab group (p=0.25), while 48% versus 17% at 12 months (p=0.007, OR 4.7; 95% CI: 1.47-15.16). The 1-2-3 year cumulative colectomy rates were 48%, 54%, 57% in the cyclosporine group, and 17%, 23%, 27% in the infliximab group. At the end of the follow-up the colectomy rate was 60% versus 30% (p=0.04, HR 2.2; 95% CI: 1.11-4.86). High level of C reactive protein (p=0.04), extensive disease (p=0.01) and no azathioprine treatment (p<0.001) were related to the risk of colectomy. CONCLUSION This study, despite being retrospective, indicates that both cyclosporine and infliximab are effective in avoiding a colectomy in steroid-refractory UC patients. During the follow-up the risk of a colectomy is higher in patients treated with cyclosporine than with infliximab.

Cancer in Crohn's Disease patients treated with infliximab: A long-term multicenter matched pair study

Background: The long‐term risk of neoplasia in Crohns disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched‐pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. Methods: A multicenter, long‐term, matched‐pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab‐treated (CD‐IFX) and 404 matched CD controls never treated with infliximab (CD‐C) studied from 1999 to 2004, was followed up for an additional 4 years (2004–2008). Cases and controls were matched for: sex, age (±5 years), CD site, follow‐up (±5 years), immunosuppressant use, and CD duration (±5 years). From 1999 to 2008 the frequency and characteristics of neoplasia were compared between CD‐IFX and CD‐C. Results: In 2008, 591 patients (304 CD‐IFX, 287 CD‐C) were in follow‐up. Matched couples included 442 patients: 221 CD‐IFX and 221 CD‐C (median follow‐up, months: 72, range 48–114 versus 75, range 44–114). From 1999 to 2008 the frequency of neoplasia among the 591 patients did not differ between CD‐IFX (12/304; 3.94%) and CD‐C (12/287; 4.19%; P = 0.95). A comparable frequency of neoplasia was also observed between the 221 matched couples (CD‐IFX: 8/221; 3.61% versus CD‐C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared associated with infliximab use. Conclusions: The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years. (Inflamm Bowel Dis 2011)

Clinical course of ulcerative colitis

AIM To provide a review of studies on prognosis in ulcerative colitis by reviewing the relevant population-based cohort studies. On the basis of incidence and population studies, ulcerative colitis has a favourable clinical course, with good quality of life, a chronic course characterized by at least one relapse, and a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe ulcerative colitis have a higher risk of colectomy, and some clinical variables may predict the diseases clinical course. Most patients respond to steroids and only a low percentage become dependent, or non-responders to steroids. Patients who have a long-lasting ulcerative colitis (>10 years) or are affected by an extensive disease have an increased risk of developing colorectal cancer, while those treated with immunosuppressants for long period of time may have an increased risk of developing lymphomas. Data on mortality in ulcerative colitis patients are not homogeneous, but if a real risk exists it is in patients with extensive or severe disease. The evidence that patients with severe ulcerative colitis are often non-smokers may explain why in one study the mortality rate was lower.

Music for colonoscopy: A single-blind randomized controlled trial

BACKGROUND Several methods have been reported to minimize patient discomfort during colonoscopy, none are currently recommended by clinical practice guidelines. We performed a single-blind randomized controlled trial to assess the efficacy of music for colonoscopy. METHODS 109 patients were randomized to music-delivering or mute headphones before and during colonoscopy. Physicians were blinded to the trial. Sedation was given on demand. Primary outcome was pain measured on linear analogue scale from 0 to 10. Secondary endpoints were the difficulty of the procedure, need of sedation, overall patient satisfaction and willingness to repeat the procedure. RESULTS Mean pain score was 5.9±2.2 in the control group vs. 3.8±1.9 in the music group (p<0.00001); correspondingly overall satisfaction and willingness to repeat the procedure were significantly improved by music and the difficulty perceived by physicians was significantly reduced. Total administered midazolam was 36mg in the control group vs. 13 in the music group (p<0.007), pethidine was 860mg vs. 465mg (p=0.07) and patients requiring sedation were 22 vs. 9, respectively (p=0.003). A multivariable analysis to adjust treatment effect for potential confounding factors confirmed the significant beneficial effect of music. CONCLUSIONS Music significantly reduces discomfort and should be routinely offered to patients undergoing colonoscopy.

Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: Final results from a large prospective multicenter study

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been reported to have a higher complication rate than that of solid lesions, but the real complication rate is unknown. Aim of the study was to identify the complication rate of endoscopic ultrasound-guided fine needle aspiration and related risk factors. METHODS Prospective multicenter study at four referral centres. Data were collected from January 2010 to July 2012, searching for all adverse events related to guided fine needle aspiration. All complications occurring up to day 90 were recorded. RESULTS 298 patients (43.9% male, mean age 63.2 ± 15.4 years) underwent endoscopic ultrasound-guided needle aspiration of pancreatic cystic lesions. Mean size was 34.1 ± 9 mm. Adverse events occurred in 18 patients (6%): mild complications in 12/18 (66.6%), and moderate complications in 6/18 (33.3%). Seven were immediate, 6 early, and 5 late. All resolved with medical therapy. CONCLUSIONS Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been found to be associated with a higher complication rate than for solid lesions; however, the risk rate is acceptable considering the complication grade and the important diagnostic role of the technique in the management of pancreatic cystic lesions.

Early post-operative endoscopic recurrence in Crohn's disease patients: Data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort

INTRODUCTION The incidence of endoscopic recurrence (ER) in Crohns disease following curative resection is up to 75% at 1 year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse. METHODS The aim of this prospective study was to evaluate the incidence of early ER 6 months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6 months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2 weeks after surgery. RESULTS Six months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p=0.04; OR 0.52, 95% CI 0.277-0.974). CONCLUSION In this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment.

The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

AIM:To evaluate the role of CARD15 mutations and smoking in the main events of Crohns disease (CD).PATIENTS AND METHODS:A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan–Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.RESULTS:A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34–51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1–2.8; HR 3.2, CI 1.8–5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52–0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4–9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8–10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1–7.3) were predictive of reoperation.CONCLUSIONS:In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.

Severe cutaneous psoriasis after certolizumab pegol treatment: report of a case.

To the Editor: Psoriasis is a papulosquamous skin disease recognized as one of the most common immune-mediated disorders (1); 90% of all cases are psoriasis vulgaris. In the past few years, anti–tumor necrosis factor alpha (TNF) agents had modified the management of severe psoriasis (2), as well as that of rheumatoid diseases and inflammatory bowel diseases. Nevertheless, several authors had reported the paradoxical development of psoriasis and psoriasiform lesions, mainly in patients with rheumatoid arthritis, using these kinds of drugs (3). An online survey showed that 63% of rheumatologists had observed psoriasis or other skin reactions during anti-TNF treatment (4). A recent review reported 18 cases of anti-TNF-induced psoriasis in patients with inflammatory bowel disease: 17 cases were infliximab induced and 1 was adalimumab induced (5). Harris et al. (6) also reported a case of adalimumab-induced psoriasis.