Daniela Scimeca

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.

Patient outcomes after total pancreatectomy: a single centre contemporary experience

INTRODUCTION Total pancreatectomy (TP) is associated with significant metabolic abnormalities leading to considerable morbidity. With the availability of modern pancreatic enzyme formulations and improvements in control of diabetes mellitus, the metabolic drawbacks of TP have diminished. As indications for TP have expanded, we examine our results in patients undergoing TP. MATERIALS AND METHODS Retrospective study of 47 patients undergoing TP from January 2002 to January 2008 was performed. Patient data and clinical outcomes were collected and entered into a database. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS Fifteen males and 32 females with a median age of 70 years underwent TP for non-invasive intraductal papillary mucinous neoplasms (IPMN) (21), pancreatic adenocarcinoma (20), other neoplasm (3), chronic pancreatitis (2) and trauma (1). Median hospital stay and intensive care stay were 11 days and 1 day, respectively. Thirty-day major morbidity and mortality was 19% and 2%, respectively. With a median follow-up length of 23 months, 33 patients were alive at last follow-up. Estimated overall survival at 1, 2 and 3 years for the entire cohort was 80%, 72% and 65%, and for those with pancreatic adenocarcinoma was 63%, 43% and 34%, respectively. Median weight loss at 3, 6 and 12 months after surgery was 6.8 kg, 8.5 kg and 8.8 kg, respectively. Median HbA1c values at 6, 12 and 24 months after surgery were 7.3, 7.5 and 7.7, respectively. Over one-half of the patients required re-hospitalization within 12 months post-operatively. CONCLUSION TP results in significant metabolic derangements and exocrine insufficiency, diabetic control and weight maintenance remain a challenge and readmission rates are high. Survival in those with malignant disease remains poor. However, the mortality appears to be decreasing and the morbidities associated with TP appear acceptable compared with the benefits of resection in selected patients.

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.

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.

Incidence of Crohn’s disease and CARD15 mutation in a small township in Sicily

Background: The incidence of Crohn’s disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant.Aim: To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population.Methods: Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 1979 to 2002 were obtained through the local health authority. NOD2/CARD15 mutations were studied in 23 out of the 29 patients with CD in Casteltermini, in 60 family members and in 64 controls. NOD2/CARD15 was also studied in 80 sporadic cases of CD disease among Sicilians outside Casteltermini and 118 healthy controls.Results: From 1979 to 2002, 29 patients with CD and 13 patients with ulcerative colitis (UC) were registered. The 6-year mean incidence of CD ranged from 8.0 to 17 new cases for every 100,000 inhabitants, whereas the mean incidence of UC ranged from five new cases to 7.8 for every 100,000 inhabitants. The allele frequencies of NOD2/CARD15 mutations (L1007finsC, G908R, R702W) were 8.7, 4.3 and 8.7%, respectively, in CD cases; 5.0, 4.2 and 3.1% in family members; 1.6, 2.3 and 3.1% in controls. In sporadic Sicilian CD patients outside Casteltermini the allele frequency was 7.5, 8.1, 6.2% whereas in control population it was 3.3, 1.6, 1.6%.Conclusions: A high incidence of CD compared with UC was observed in this small town in Southern Italy. The frequency of NOD2/CARD15 mutations in CD is similar to other Caucasian population studied so far.

Minimizing infliximab toxicity in the treatment of inflammatory bowel disease

BACKGROUND Infliximab is a widely used biological agent for the treatment of inflammatory bowel disease, and has a favorable risk/benefit ratio. AIM It is useful to know that patients treated with infliximab are exposed to developing adverse events that could be reduced with a prudent and a rational clinical approach and by optimizing the treatment protocol. METHODS PubMed (including Epub) was searched in October 2006 and again in March 2007. RESULTS The high immunogenic potential of infliximab determines the antibodies that inhibit the effect of infliximab and the appearance of subsequent acute and delayed infusion reactions. Infliximab has an immunomodulatory effect, thus increasing the risk of serious and latent infections. Screening for tuberculosis, HBV, opportunistic or latent infections, heart failure, and haematological, neurological and hepatological disorders must be performed before infliximab therapy. There is no definitive evidence that infliximab increases the risk of neoplasia. Mortality in infliximab-treated patients does not appear increased compared to the controls. CONCLUSIONS Infliximab safety is similar to that of conventional immunomodulators and patients treated had similar rates of mortality, neoplasm and lymphoma as patients not treated with infliximab. Patients treated with infliximab have an increased risk of serious infections but it is not related to infliximab therapy.

S1214 Early Post-Operative Endoscopic Recurrence in Crohn's Disease in an Italian Multicentric Cohort

Introduction: Previous studies have suggested that the long-term outcome of patients with perianal Crohns disease (CD) is quite poor and that a very high proportion of cases, up to 50%, eventually need a permanent digestive diversion for the management of their condition (1). Aims & Methods: Our aim was to address the long-term outcome of patients with perianal CD (p-CD), as well as drugs necessary for their management, compared with CD patients without perianal CD (Np-CD). Data were gathered from the prospective database of the IBD outpatient clinic of the gastroenterology Department of two University Hospitals. Adult patients with a diagnosis of CD before 2008 and a minimum follow-up time of one year were included. Results: A total of 599 CD patients (age range 17-85) were included. Mean follow-up time was 9.6 years. One hundred fifty-three patients (25.5%) had p-CD. p-CD patients were treated with AZA in 82.4% and with IFX in 43.4% of cases, as compared with 51% and 9.3% of Np-CD respectively (p< 0.001 in both cases). The rate of resective surgery was similar in both groups, 36% in p-CD and 38.2% in Np-CD (p= 0.9). Surgical diversion by permanent ileostomy was necessary in 3.9% (n= 6) of p-CD. Conclusion: A 25.5% of our CD patients are affected by perianal disease. AZA and IFX were significantly more necessary in this subset of patients than in CD patients without perianal disease. However, there was no difference in the ratio of resective surgery and permanent surgical diversion by ileostomy was rare, only necessary in 3.9% of p-CD patients. It is possible that immunosuppressive drugs and biologics have lowered the need for permanent ileostomy in this subset of patients. Reference: 1. Galandiuk S. Ann Surg 2005.

S1297 When to Operate or Observe Branch Duct Intraductal Papillary Mucinous Neoplasms (IPMN-Br): Evaluation of Consensus Guidelines

BACKGROUND: The current Consensus Guidelines for management of IPMN-Br recommend surgical resection of suspected IPMN-Br with cyst size >3 cm cysts irrespective of symptoms, and 3 cm, and 65% <3 cm in size. Among IPMN <3 cm, 72 % (28/39) had associated worrisome features. The prevalence of high-risk lesions in our study was 35% (21/60). A total of 82 % (49/60) of IPMN-Br met guidelines recommendation for surgical resection including 57% (18 of 26) of low-risk lesions and 100% (21/21) of highrisk lesions. All 11 cases of IPMN-Br that would have been recommended for conservative management were low-risk lesions. Sensitivity, specificity, positive predictive value, negative predictive value consensus guidelines for correctly defining high and low risk IPMN-Br was 100%, 28%, 43 %, 100%, respectively. CONCLUSIONS: Application of Consensus Guidelines to our patients would have recommended surgical resection to all histology proven high-risk IPMN-Br. All IPMN-Br which would have recommended for conservative management, were histologically low-risk lesions. The risk of high risk pathology among <3 cm IPMN without other worrisome features, is almost nonexistent and these lesions may selected for observation.

S1299 Glycemic Control in Patients Post Total Pancreatectomy for Intraductal Papillary Mucinous Neoplasm (IPMN)

BACKGROUND: The current Consensus Guidelines for management of IPMN-Br recommend surgical resection of suspected IPMN-Br with cyst size >3 cm cysts irrespective of symptoms, and 3 cm, and 65% <3 cm in size. Among IPMN <3 cm, 72 % (28/39) had associated worrisome features. The prevalence of high-risk lesions in our study was 35% (21/60). A total of 82 % (49/60) of IPMN-Br met guidelines recommendation for surgical resection including 57% (18 of 26) of low-risk lesions and 100% (21/21) of highrisk lesions. All 11 cases of IPMN-Br that would have been recommended for conservative management were low-risk lesions. Sensitivity, specificity, positive predictive value, negative predictive value consensus guidelines for correctly defining high and low risk IPMN-Br was 100%, 28%, 43 %, 100%, respectively. CONCLUSIONS: Application of Consensus Guidelines to our patients would have recommended surgical resection to all histology proven high-risk IPMN-Br. All IPMN-Br which would have recommended for conservative management, were histologically low-risk lesions. The risk of high risk pathology among <3 cm IPMN without other worrisome features, is almost nonexistent and these lesions may selected for observation.