Giovanna Margagnoni

Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive factors.

In recent years mucosal healing has emerged as an important therapeutic goal for patients with inflammatory bowel disease. Growing evidence suggests that achieving mucosal healing can improve patient outcomes and, potentially, alter the course of the disease. Drugs currently used in the management of inflammatory bowel disease are potentially able of inducing and maintaining mucosal healing, but the effect size is difficult to assess because of different definitions of mucosal healing, differences in study designs, and timing of endoscopic evaluation. Mucosal healing has been studied extensively in the biologic era. Data available from different sources, such as controlled trials and observational studies, show that anti-TNFα therapies can induce rapid and sustained mucosal healing in a variable percentage of patients with Crohns disease and ulcerative colits. No controlled study has been designed to identify possible predictors of mucosal healing. Some clinical characteristics such as extensive disease, young age at diagnosis, and smoking status may be predictive of a more aggressive clinical course and, presumably, of a reduced clinical and endoscopic response to therapy. Changes and normalization of C-reactive protein and faecal calprotectin may be useful tools to predict outcomes, guide the timing for endoscopic evaluation and, possibly, reduce the need of endoscopic evaluation in assessing mucosal healing.

IL-1β-511 and IL-1RN*2 polymorphisms in inflammatory bowel disease: An Italian population study and meta-analysis of European studies

BACKGROUND Several studies have tried to find possible associations between genetic polymorphisms and inflammatory bowel disease prevalence and/or phenotype. Our objectives were to test the frequency and phenotypic association of two polymorphisms of the interleukin-1 pathway, IL-1beta-511 and IL-1RN*2, in inflammatory bowel disease patients and controls from an Italian population, and to compare our data with previously published similar studies in Europe. METHODS We screened 290 inflammatory bowel disease patients (178 ulcerative colitis and 112 Crohns disease) and 106 controls for IL-1beta-511 and IL-1RN*2 polymorphisms by polymerase chain reaction (PCR)-based methods. The prevalence of the IL-1beta-511 and IL-1RN*2 polymorphisms in European inflammatory bowel disease patients was calculated by a meta-analysis of previously published studies using the Mantel-Haenszel method. RESULTS No correlation between the IL-1 polymorphisms and inflammatory bowel disease prevalence was found in our study population. Crohns disease patients with the IL-1beta-511 mutation had a higher rate of complicated disease. A trend for an association between the IL-1RN*2 mutation and a higher risk for inflammatory bowel disease has been found only in studies with Northern European populations. CONCLUSIONS The IL-1beta-511 mutation can be associated with complex disease behaviour in Italian Crohns disease patients. The IL-1RN*2 mutation may play a role in Northern European people with inflammatory bowel disease.

Outcome and risk of recurrence for endoscopic resection of colonic superficial neoplastic lesions over 2 cm in diameter

BACKGROUND Large colorectal superficial neoplastic lesions are challenging to remove. This study aimed to assess the outcomes of routine endoscopic resection of large (≥2 cm and <3 cm) and giant (≥3 cm) lesions. METHODS From 4587 endoscopic resections, 265 (5.7%) large and giant lesions were removed in 249 patients. We retrospectively analyzed 125 patients (141 endoscopic mucosal resection, 73 large and 68 giant lesions) with a follow-up of 6-12 months. Rate of en bloc and piecemeal resection, recurrence and risk factors were analyzed. RESULTS En bloc was performed in 92 cases (65.2%) and piecemeal resection in 49 (34.8%). A complete endoscopic resection was achieved in 139 cases (98.5%) with radical resection in 84/139 cases (60.4%). Argon plasma coagulation was applied in 18/141 lesions (12.8%). A recurrence occurred in 16/139 lesions (11.5%). The risk of recurrence at one year was significantly higher for giant than large lesions (p=0.03). The recurrence risk was higher in treated than in non-argon plasma coagulation treated lesions (p=0.01). CONCLUSIONS endoscopic mucosal resection is a safe and effective routine treatment for large superficial neoplastic lesions. The risk factors for recurrence include giant size, non-protruding morphology, piecemeal technique and argon plasma coagulation.

Is proliferative colonic disease presentation changing

AIM To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods. METHODS CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed. RESULTS Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07). CONCLUSION The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.

The Time Course of Diagnostic Delay in Inflammatory Bowel Disease Over the Last Sixty Years: An Italian Multicentre Study

Background and Aims Inflammatory bowel disease [IBD] patients are still under-diagnosed or diagnosed with serious delay. We examined whether diagnostic delay [DD] in IBD has changed over the last 60 years, and explored the risk factors of longer DD. Methods In total, 3392 IBD patients recorded in the registry of four IBD Italian centres were divided according to the year of diagnosis into a historical cohort [HC: 1955-84] and modern cohort [MC: 1985-2014]. DD, i.e. time lapse between onset of symptoms indicative of IBD and definitive diagnosis, was divided into four sub-periods [0-6, 7-12, 13-24, >24 months], which were correlated with age and disease location/behaviour at diagnosis. Results Median DD in IBD was 3.0 months, it was significantly [P < 0.0001] higher in Crohns disease [CD] [7.1 months] than in ulcerative colitis [UC] [2.0 months], and did not differ either between the HC and the MC or over the last three decades. However, the proportion of patients with a DD>24 months was significantly [P < 0.0001] higher in the HC [26.0%] than in the MC [18.2%], and the same trend was evident over the last three decades [1985-94: 19.9%; 1995-2004: 16.4%; 2005-14: 13.9%; P = 0.04]. At logistic regression analysis, age at diagnosis >40 years (CD: odds ratio 1.73, 95% confidence interval [CI] 1.31-2.28, P < 0.0001; UC: 1.41, 95% CI 1.02-1.96, P = 0.04) and complicated disease at CD diagnosis [1.39, 95% CI 1.06-1.82, P = 0.02] were independently associated with a DD>24 months. Conclusions DD duration has not changed over the last 60 years in Italy, but the number of IBD patients with a longer DD significantly decreased. Older age at diagnosis and a complicated disease at CD diagnosis are risk factors for longer DD.

DOP093 Characterisation of incident cases of cancer in inflammatory bowel disease: A prospective multicenter matched-pair IG-IBD study

DOP093 Characterisation of incident cases of cancer in inflammatory bowel disease: A prospective multicenter matched-pair IG-IBD study L. Biancone1 *, C. Petruzziello1, A. Armuzzi2, M.L. Scribano3, R. D’Inca4, C. Papi5, L. Spina6, L. Guidi2, A. Kohn3, E. Calabrese1, G. Condino1, S. Onali1, F. Mocciaro7, R. Monterubbianesi3, P. Alvisi8, W. Fries9, G. Riegler10, F. Castiglione11, I. Frankovic4, G. Margagnoni5, R. Di Mitri7, G. Meucci12, F. Rogai13, S. Ardizzone14, A. Orlando15, F. Pallone1. 1Universita di Roma Tor Vergata, Medicina dei sistemi, cattedra di Gastroenterologia, Roma, Italy, 2Universita Cattolica, CIC, Roma, Italy, 3A.O.San Camillo Forlanini, Gastroenterology Unit, Rome, Italy, 4University of Padova, Gastroenterology Department, Padova, Italy, 5AO S. Filippo Neri, UOC GE/Hep, Roma, Italy, 6Universita S. Donato, Gastroenterologia, Milano, Italy, 7ARNAS Civico-Di Cristina-Benfratelli Hospital, Gastroenterology and Endoscopy Unit, Palermo, Italy, 8Ospedale Maggiore, Pediatria, Bologna, Italy, 9Universita di Messina, Medicina Interna, Messina, Italy, 10Seconda Universita Napoli, SUN, Napoli, Italy, 11Universita “Federico II” di Napoli, Gastroenterologia, Napoli, Italy, 12S. Giuseppe Hospital, Gastroenterology, Milano, Italy, 13AOU Careggi, Largo Brambilla, Gastroenterologia, Firenze, Italy, 14Luigi Sacco University Hospital, Gastroenterology Department, Milano, Italy, 15Ospedale Cervello, Medicina Interna, Palermo, Italy

[Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point].

In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohns disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed.

Impatto dei fattori ambientali sul decorso delle malattie infiammatorie croniche dell’intestino: quali evidenze?

Riassunto. Identificare fattori ambientali che possano in fluenzare il decorso delle malattie infiammatorie croniche dell’intestino (MICI) e di grande interesse poiche riuscendo a intervenire su questi si potrebbe migliorare la prognosi dei pazienti. Nessun fattore ambientale si e dimostrato avere un nesso lineare di causa-effetto con il riacutizzarsi di malattia, ma numerosi fattori ambientali (fumo, dieta, farmaci, stress, ecc.) sembrano giocare un ruolo plausibile nell’influenzare l’andamento clinico delle MICI. Lo scopo di questa revisione e quello di descrivere le attuali evidenze presenti in letteratura sull’impatto di diversi fattori ambientali sul decorso a lungo termine delle MICI e di formulare raccomandazioni pratiche che possano essere di aiuto al medico e al paziente nella gestione delle MICI. Parole chiave. Colite ulcerosa, decorso clinico, fattori ambientali, malattia di Crohn, malattie infiammatorie croniche intestinali. Environmental factors and clinical course of inflammatory bowel disease: which evidences? Summary. Identify environmental factors that can influence the course of inflammatory bowel disease (IBD) is of great interest since managing on these factors might improve the prognosis of patients. No environmental factor has been shown to have a linear cause-and-effect link with the relapse of the disease, but many environmental factors (smoking, diet, medications, stress, etc.) seem to play a plausible role in influencing the clinical course of IBD. The aim of this review is to describe the current evidence of the impact of different environmental factors on the long-term course of IBD and to give practical indications that can help doctors and patients in the management of IBD.

Mo1264 Clinical Characteristics of Inflammatory Bowel Disease May Influence the Cancer Risk When Using Immunomodulators: Incident Cases of Cancer in a Multicenter Case-Control Study

anesthesia at the Surgical Department-San Camillo Forlanini Hospital from 1980 to 2012. Recto-vaginal and recto-urethral fistulas were excluded. The follow-up was calculated from diagnosis to the onset of a NO or to the end of observation. Patients were divided in 3 cohorts according to the time of diagnosis (A: 1980-’89, B: 1990-’99, C: 2000-’12). Results: 229 (47% females, median age 34 [range 9 74]) patients with perianal fistulas were analyzed; 19 with rectovaginal or recto-urethral fistulas were excluded. Out of 210 patients: 56 (27%) had ileal disease, 55 (26%) colonic, 98 (47%) ileocolonic involvement. Complex fistulas were diagnosed in 181 patients (160 transphincteric, 10 suprasphincteric, 11 extrasphincteric), 30 had simple fistulas (5 superficial, 25 intersphincteric), 103 rectal involvement. The follow up was 72 months, within this period 99% of patients underwent 1 surgical procedure, 58% underwent 2 or more procedures. The cumulative probability of disease free from NOs was 0.7, not influenced by the type of fistula, by the age at diagnosis or by the sex, and was not significantly different for the three cohorts. Conversely, the risk of NO was significantly related to localization of disease (colonic vs ileal disease, p = 0.001) and to rectal involvement (p = 0.002). Two or more surgical procedures were related to an increased risk of NO compared to a single one (p < 0.001). The risk was not significantly reduced by immunosuppressive or biological therapy. At multivariate analysis, the risk of NO was independently predicted by the number of surgical procedures (P= 0.009) and colic disease (P= 0.04). Conclusions: Our results suggest that in patients with perianal CD, the risk of NO is high, not influenced by the type of fistula but significantly related with disease localization, rectal involvement and need of more than one surgical procedure. Despite the introduction of biological and immunosuppressive treatments, the probability of negative outcomes did not change.

P.02.9 INCIDENT CASES OF CANCER IN IBD: CLINICAL CHARACTERISTICS OF IBD VS IMMUNOMODULATORS IN A PROSPECTIVE MULTICENTER CASE-CONTROL STUDY

effective non invasive monitoring could help clinicians in the management of Crohn’s disease (CD) patients treated with adalimumab. Aim of the study is to identify early predictors of long term clinical response during treatment with adalimumab. Material and methods: 68 patients with moderate to severe CD referred to a nurse-led outpatient clinic were prospectively enrolled from January 2009 to December 2011. All patients were treated with a 160–80 mg every other week (eow) induction protocol and maintained with 40 mg eow. Clinical activity (Harvey Bradshaw Index – HBI), faecal lactoferrin (LF), C reactive protein (CRP) were assessed at baseline, at the end of induction and 6 and 12 months after. Results: After induction, 42.3% of patients were in clinical remission and 37% responded showing at least a 2-points decrease in HBI. LF and CRP decreased significantly after the induction period (p<0.001 and p=0.02 respectively) and remained in the normal range throughout the maintenance period. 63% of patients in remission at the end of induction maintained remission at one year (p=0.02, OR=0.15), on the contrary only 36% of patients still active after induction were able to reach clinical remission at twelve months (p=0.009, OR=6.96). After twelve months 58.3% of patients were in remission according to HBI. 61% of patients achieving LF normalization at the end of induction were in clinical remission at one year (p=0.004, OR=0.06), while only 39% of patients with abnormal LF (p=0.004, OR=15.45). 95% patients with normal CRP after induction were in clinical remission at one year (p=0.003, OR=0.06), while only 4.5% of those showing abnormal CRP (p=0.003, OR=15.75). Linear regression models found that clinical remission combined with early CRP and LF normalization after induction is the best predictor of maintenance of clinical remission at one year. Conclusions: Clinical activity and biochemical markers performed at the end of induction proved to be reliable in predicting the course of CD in the long term maintenance treatment with adalimumab, therefore clinical and laboratory monitoring should be performed routinely in these patients.