- Email: [email protected]
P094 CLINICAL, SURGICAL AND GENETIC RISK FACTORS FOR DEVELOPMENT OF POUCHITIS FOLLOWING IPAA FOR ULCERATIVE COLITIS
Abstracts of ECCO Congress, Innsbruck, Austria, 1—3 March 2007 P091 IBD AND LIPID PARAMETERS: ROLE OF INFLAMMATION G. Romanato 1 , M. Scarpa 2 , I. Angriman 2 , R. Marin 1 , C. Ruffolo 2 , S. Basato 2 , S. Zannoni 1 , S. Zambon 1 , T. Filosa 2 , F. Pilon 2 , L. Polese 2 , E. Manzato 1 . 1 Clinica Medica I, Dipartimento di Scienze Mediche e Chirurgiche, University of Padova; 2 Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, University of Padova Objective: The aim of this study was to evaluate the relationships between inflammatory parameters and lipid and phospholipids fatty acid (FA) profile in patients with ulcerative colitis (UC) and Crohn disease (CD). Method: Ninety consecutive patients, admitted for surgery for UC or CD between December 2004 and April 2006, were enrolled in this cross sectional study. Disease activity (Seo and CDAI index), diet, inflammatory parameters, lipid profile and serum, subcutaneous and omental fatty acids (FA) phospholipids composition were assessed. Lipid and plasma phospholipids fatty acid profiles were also evaluated in a group of 33 healthy subjects, enrolled as controls. Data were expressed as mean ± standard deviation and Pearson correlation and t test were used. Result: Total and LDL cholesterol were significant lower in IBD patients compared to healthy controls (total cholesterol 163±43 vs 207±41 mg/dl, p=0.0001; LDL 92±37 vs 129±38 mg/dl, p<0.01). In the phospholipids fatty acid profile only the stearic acid (18:0), was significantly lower in the IBD patients (12,38 vs 14,12%). No correlation between erythrocytes sedimentation rates and lipid and phospholipids fatty acid was observed. On the contrary Creactive protein (CRP) correlated significantly with HDL (r=-0.24, p=0.034), palmitic acid (16:0) (r=+0.49, p=0.000) and saturated fatty acids (r=+0.28, p=0.002), dihomo-gamma-linolenic acid (20:3 n6) (r=-0.26, p=0.035), docosapentaenoic acid (22:5 n3) (r=-0.27, p=0.033), arachidonic acid (20:4 n6) (r=-0.26, p=0.041). Conclusion: The lipid profile in IBD patients seems to reflect a condition of malabsorption. The weak correlations between CRP and some fatty acids may suggest that the inflammatory status of IBD patients involves also the serum phospholipids fatty acids composition. Modifications of fatty acid composition (e.g. with n3 fatty acid supplementation) could modify the effects of inflammation on these patients.
P092 AUTOLOGOUS STEM CELL TRANSPLANTATION IN MODERATE-SEVERE REFRACTORY CROHN' S DISEASE: THE MILAN EXPERIENCE WITHOUT CD 34+ CELL SELECTION A. Cassinotti 1, S. Ardizzone 1 , C. Annaloro 2 , F. Onida 2 , D. Trabattoni 3 , A. Della Volpe 2 , C. Vener 2 , G. Maconi 1 , S. Greco 1 , G. Lambertenghi Deliliers 2, M. Clerici 3 , G. Bianchi Porro 1 . 1 Department of Clinical Science, Gastroenterology Unit, L. Sacco University Hospital, Milan, Italy; 2 Bone Marrow Transplantation Centre, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy; 3 Chair of Immunology, University of Milan, Milan, Italy Background and aims: Autologous haematopoietic stem cell transplantation (aHSCT) with CD34+ cell selection has recently been used to treat refractory Crohn' s disease (CD), showing good safety and promising efficacy. We investigate the safety and efficacy of aHSCT without CD34+ cell selection in refractory CD. Patients and Methods: Four patients (3 males, 1 female; age 26-45 years) with active moderate-severe CD (median CDAI 316), refractory or intolerant to multiple drugs including infliximab, were enrolled. Unselected PBSCs were collected after mobilisation with CTX 1.5 g/m2 and G-CSF 10 g/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit ATG 2.5 mg/kg on days -4 to -2. Primary end point were toxicity and clinical remission (CDAI < 150) at 3 months. Secondary end point were endoscopic response (SES-CD) at 3 months and modulation of T reg (CD4/CD25/Foxp3) cells, a subset of lymphocyte with inhibitory actions, measured at baseline, 3 and 6 months. Results: No improvement or slight worsening was observed after mobilisation (median CDAI 335, range 258-404). At the third month, the primary end-point was reached in all patients, with a median CDAI of 85 (range 56-102) despite discontinuation of all medication, apart from antibiotics in two patients with perianal fistula. Endoscopic scores improved in 3/4 patients. No unexpected serious adverse events were observed, except for a new perianal abscess after mobilisation in one patient, idiopathic pericarditis in another and hemorrhagic cistitis by Staph aureus in an other patient, all quickly treated with conservative therapy. At 6 months CD4/CD25/Foxp3 cells were lesser in the unique patient that didn' t reach also endoscopic remission. Conclusion: Unselected CD34+ cells transplantation is safe overall and can induce remission in previous refractory patients. Interesting immunomodulatory effects are suggested. Further recruitment and long-term results are ongoing.
27 P093 RESTORATIVE PROCTOCOLECTOMY FOR ULCERATIVE COLITIS: IMPACT ON LIPID METABOLISM AND ON TISSUTAL AND SERUM FATTY ACIDS M. Scarpa 1 , G. Romanato 2 , E. Manzato 2 , C. Ruffolo 1 , R. Marin 2 , S. Basato 1 , S. Zannoni 2 , S. Zambon 2 , T. Filosa 1 , F. Pilon 1 , L. Polese 1 , I. Angriman 1 . 1 Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, University of Padova; 2 Clinica Medica I, Dipartimento di Scienze Mediche e Chirurgiche, University of Padova Objective: Even if intestinal absorption is not directly impaired ulcerative colitis (UC) deserves important metabolic implications. In fact, chronic inflammation and accelerated intestinal transit may significantly influence lipid metabolism. Restorative proctocolectomy (RPC) usually obtains the resolution of inflammatory process but the accelerated transit may persist The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids of UC patients after RPC. Method: Fifteen patients who underwent RPC for UC between December 2004 and April 2006 were enrolled. Disease activity, diet, inflammatory parameters, lipid profile and composition of fatty acids (FA) of serum phospholipids were assessed at RPC and at ileostomy closure. In 9 patients at RPC, and in 10 at the ileostomy closure, FA composition of phospholipids of subcutaneous adipose tissue were also evaluated. Fifteen sex-and-age matched healthy subjects were enrolled as controls. Data were expressed as median (range) and Wilcoxon paired- and Mann-Whitney U tests were used. Results: The median interval between RPC and ileostomy closure was 6 (29) months. In UC patients total cholesterol was significantly lower than in healthy subjects at RPC and at ileostomy closure. During that interval the inflammatory parameters improved as well as lipid profile (median HDLcholesterol: from 43 (19-65) to 56 (25-84) mg/dl, p<0.01; median LDLcholesterol: from 100 (26-160) to 52 (24-139) mg/dl, p=0.01). At ileostomy closure serum arachidonic acid and docosaesaenoic acid levels were increased compared to levels at RPC (p=0.04 and p=0.05, respectively), while serum oleic acid level was decreased (p=0.02). No significant alteration in serum n-3 FA precursors was observed in UC patients in the interval between RPC and ileostomy closure. On the contrary 22:6 n3 appeared to be lower in UC patients at ileostomy closure compared to healthy controls (p<0.01). No significant differences in the composition of FA of subcutaneous adipose tissue were observed between RPC and ileostomy closure. Conclusion: The increase of serum percentage of arachidonic acid after RCP might be explained by a lower utilization for inflammatory process The observed reduction of LDL cholesterol could be an index of malabsorption and was probably due to the persistency of an accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.
P094 CLINICAL, SURGICAL AND GENETIC RISK FACTORS FOR DEVELOPMENT OF POUCHITIS FOLLOWING IPAA FOR ULCERATIVE COLITIS M. Ferrante 1, S. Declerck 1 , T. Koopman 1 , M. Pierik 1 , P. Rutgeerts 1 , G. Van Assche 1 , A. D' Hoore 2 , F. Penninckx 2 , S. Vermeire 1 . 1 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2 Department of Abdominal Surgery, University Hospital Gasthuisberg, Leuven, Belgium Background & Aims: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The pathogenesis is unclear, although faecal stasis and bacterial overgrowth are judged important etiologic factors. We therefore investigated the role of microbial pattern recognition receptor genes in prediction of pouchitis after IPAA. Methods: A total of 132 (77 male) consecutive patients with IPAA for UC were studied. Median (interquartile range, IQR) age at surgery was 39.8 (31.6-47.8) years. Fourteen percent were active smokers at surgery, while 49% percent had never smoked. Fifty-two percent had extra-intestinal manifestations (EIM), 73% had extensive colitis, 6% had backwash ileitis. Surgery was performed in 1, 2 or 3 stages in, respectively, 16%, 69% and 15% and laparoscopic assisted in 47%. All patients were genotyped by PCR-RFLP for 56 non-synonymous polymorphisms in Toll Like Receptors (TLRs) 1-10, 3 common CARD15 mutations, TNF -G308A, CD14 —C260T and a variable number tandem repeat in intron 2 of IL1-RA. Diagnosis of pouchitis was based on clinical, endoscopic and histological criteria. Pouchitis was defined acute relapsing if patient had 3 or more acute episodes of pouchitis; and chronic if symptoms lasted for more than 4 weeks, despite a full dose of standard therapy. Results: With a median (IQR) follow-up of 6.5 (3.3-9.8) years, 64 patients (48%) developed pouchitis (24 acute, 11 relapsing and 29 chronic). One patient needed pouchectomy for pouch necrosis. Median (IQR) duration between restoration of transit and first pouchitis episode was 12 (5-28) months. In multivariate analysis young age at surgery (36.0 vs. 42.5 years, Odds ratio (OR) 1.04, 95% CI 1.01-1.08, p=0.015), presence of EIM (59% vs. 38%, OR 2.25, 95% CI 1.21-5.30, p=0.014) and presence of a T allele in TLR1 S87I (57%
28 vs. 41%, OR 2.13, 95% CI 1.02-4.45, p=0.044) were independently associated with pouchitis, and with faster onset of pouchitis (Kaplan-Meier respectively, p=0.017, p=0.001 and p=0.066). Chronic pouchitis was inversely associated with disease duration before surgery (3.6 vs. 7.8 years, OR 0.91, 95% CI 0.830.99, p=0.036) and presence of a CD14 -260C allele (36% vs. 68%, OR 0.23, 95% CI 0.06-0.83, p=0.025). Discussion: Young age at surgery, presence of EIM and TLR1 S87I were independently associated with early development of pouchitis in UC. Short duration of disease and presence of CD14 -260C allele were associated with chronic pouchitis. Both TLR1 and CD14 are co-factors of the lipopolysaccharide receptor complex and support the hypothesis that bacterial recognition is important in the onset of this complication after IPAA.
P095 LONG-TERM SAFETY OF AZATHIOPRINE TREATMENT IN INFLAMMATORY BOWEL DISEASE: RESULTS FROM A SINGLE REFERRAL CENTER K. Katsanos 1,2 , M. Ferrante 1, H. Fidder 1 , L. Henckaerts 1, D. Christodoulou 2 , G. Van Assche 1 , E. Tsianos 2, S. Vermeire 1 , P. Rutgeerts 1 . 1 Department of Gastroenterology, University of Leuven Hospitals, Leuven, Belgium; 2 1st Division of Internal Medicine & Hepato-Gastroenterology Unit, University Hospital of Ioannina, Greece Background: There is conflicting data regarding long-term safety including risk of malignancy in inflammatory bowel disease (IBD) patients receiving azathioprine (AZA). Aim: To describe the long-term safety including the prevalence of malignancies in a large cohort of IBD patients treated with AZA in a single referral center. Patients and Methods: Retrospective data collection from a computerized database of 1815 IBD patients (1355 Crohn' s [CD], 447 ulcerative colitis [UC], 13 indeterminate colitis [IC]). All patients who previously received or were currently taking AZA were identified and reviewed for occurrence and type of malignancies. Results: We identified 729 IBD patients previously or currently on AZA (555 CD, 169 UC, 5 IC). Median disease duration was 12 years (interquartile range [IQR] 7-19 years) and follow up on AZA/6-MP was (median, IQR) 7.1 (4.49.7) years. Combination therapy with Infliximab (IFX) was administered in 232 patients (208 CD). Before and during AZA segmental bowel resection was performed in 190 (26.2%) patients and total colectomy in 74(10.2%). A total of 15 patients [2%] (12 CD, 3UC/12 females, 3 males) were diagnosed with 17 cancers, all extra-intestinal but no lymphoma. Thirteen patients were on concomitant IFX. There was no significant difference in age, gender, duration of disease, and duration of AZA therapy between AZA-cancer and AZA non-cancer patients (data not shown). In the whole AZA cohort mortality rate was 0.82% (6/729 patients) while all AZA-cancer patients were alive on latest follow up. We identified 88/729 (12%) patients with AZA-related bone marrow toxicity (BMT) necessitating dose adjustment or interruption of therapy. Infections were diagnosed in 27 BMT patients (30%), 8 of them were severe and 4/8 were of viral origin. Conclusions: In this large single center cohort of 729 IBD patients treated with AZA, the mortality rate was 0.82% and prevalence of cancer was 2%, all extra-intestinal. Duration of therapy, disease duration, age, presence of BMT were not associated with a higher cancer risk. BMT was associated with infections in a third of patients and half of severe infections were viral.
P096 LIPID AND PHOSPHOLIPID PROFILE SIX MONTHS AFTER ILEO-COLONIC RESECTION FOR CROHN' S DISEASE G. Romanato 1 , M. Scarpa 2 , C. Ruffolo 2 , R. Marin 1 , S. Zannoni 1 , S. Zambon 1 , S. Basato 2 , T. Filosa 2 , F. Pilon 2 , I. Angriman 2 , E. Manzato 1 . 1 Clinica Medica I, Dipartimento di Scienze Mediche e Chirurgiche, University of Padova; 2 Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, University of Padova Objective: The patients affected by Crohn' s disease (CD) present often with a malnutrition status, that may persists even after the acute phase of disease. The aim of this prospective study was to evaluate which effect may have surgical induced remission on the lipid and phospholipids profile. Method: Thirty-seven patients, who underwent ileo-colonic resection for CD between December 2004 and April 2006, were enrolled in this prospective study. Anthropometric parameters, disease activity, diet, inflammatory parameters, lipid profile and serum phospholipids fatty acids (FA) composition were assessed at ileo-colonic resection and after 6 months. Data were expressed as mean (range) and t-test for paired data and Spearman correlations between percent variation (delta%) were used. Result: The mean interval between resection and control was 6 (4-9) months. During this interval CRP serum levels decreased, even if not significantly,
Poster Presentations and albumin levels were significantly increased (38.0 vs 43.1g/l, p=0.015). In lipid profile the only modification was a significant increase of HDL cholesterol (from 48±19 to 57±19 mg/dl, p<0.01). Serum arachidonic acid (20:4 n6) and adrenic acid (22:4 n6) decreased significantly after 6 months of interval. A significant correlation between the delta% of weight and eicosanoic (20:1 n9) (r=-0.93, p= p<0.01) and eicosapentaenoic acid (EPA) (20:5 n3) (r=0.82, p=0.02) was observed. The delta% of CRP directly correlated with delta% of oleic acid (18:1 n9) (r=0.82, p=0.02) and with those of palmitoleic acid (16:1 n7) (r=0.82, p=0.02), and inversely with those of stearic acid (18:0) (r=-0.86, p=0.01). Conclusion: The restoration of the intestinal physiological properties after ileo-colonic resection is probably the cause of HDL cholesterol increase since the HDL proteins are produced in the intestine. The serum fatty acid modifications, that were observed after the 6 months follow up, could be attributed to dietary modifications and to modification of the activities of the liver enzymes that regulates fatty acid metabolism (i.e. elongase and desaturase). In fact, the activity of these enzymes is strictly related to the disease activity.
P097 NATURAL HISTORY OF CYTOMEGALOVIRUS INFECTION IN A COHORT OF PATIENTS DIAGNOSED WITH MODERATE-SEVERE ULCERATIVE COLITIS V. Criscuoli 1 , M.R. Rizzuto 2 , E. Gallo 2 , M.C. Renda 3 , A. Orlando 1 , L. Montalbano 4 , M. Cottone 1 . 1 Medicine, Pneumology and Physiology of Human Nutrition Department. "V.Cervello" Hospital Palermo; 2 Institute of Pathology, "V.Cervello" Hospital Palermo; 3 Ematology II Division, "V.Cervello" Hospital Palermo; 4 Gastroenterology Division, "V.Cervello" Hospital Palermo Aim of the study: The relationship between Cytomegalovirus (CMV) infection and Inflammatory Bowel Disease (IBD) is well-known since many years. Prevalence data reported are different on the basis of diagnostic methods used. The aim of this study is to evaluate the natural history of CMV infection on a series of 25 patients (pts) admitted to our department from 1999 to 2006 for a reactivation of ulcerative colitis, in which the histopathological search for CMV resulted positive. Patients and Methods: 110 consecutive patients with moderate-severe ulcerative colitis flare-up ( according to the Truelove criteria) were admitted to the Medicine Department of V.Cervello Hospital in Palermo. On admission a CMV search was conducted performing an haematoxylin and eosin (H&E) stain on rectal biopsies searching for a tipical cytomegalic cell and inclusion bodies and Immunoistochemical (ICH) assay to detect viral protein. Among 110 patients, 25 (9 women and 16 men) resulted positive for CMV infection (both H&E and ICH). After recovery the patients were followed -up clinically every three months and histologically every two years by multiple biopsies obtained during colonoscopic assessment. The specimens collected (in all 260) were examined with E&O, ICH and tissue nested PCR for CMV DNA using primer pairs specific for Cytomegalovirus. Results: The median clinical and endoscopic follow-up was 40 months (9-72). Among 25 pts five were lost at follow-up (one died due to a cause not related to ulcerative colitis, four were operated on for severe disease). Among the 20 pts with complete follow-up, 5 (20%) pts were found positive for CMV DNA in intestinal specimens. Eight (40%) experienced at least one moderate-severe flare-up of colitis. In 3 out of 8, CMV DNA was detected by PCR in intestinal tissue (37.5%). Among the 12 patients who maintained clinical remission CMV DNA was detected in two (16%). The number of cases was too small to detect a statistical significance. Two out of 3 patients positive for CMV genome that experienced a colitis attack and one out of two patients positive for CMV in remission were maintained with immunosuppressant. Conclusions: Our preliminary results suggest that the CMV may remain in the colon despite remission. There was a slight more higher relapse in patients with detected CMV by nested PCR in intestinal tissue samples after recovery of a colitis. Prospective and controlled studies in large cohorts of IBD patients are needed to confirm this observation.
P098 FERTILITY AND SEXUAL ACTIVITY DISORDERS IN MALE PATIENTS WITH INFLAMMATORY BOWEL DISEASE D. Checchin 1 , A. Garolla 2 , M. Lisiero 3 , M. Martinato 1 , R. D' Incà 1 , C. Foresta 2, G.C. Sturniolo 1 . 1 Department of Surgical and Gastroenterological Sciences, University of Padua; 2 Department of Hystology, Microbiology and Medical Biothecnologies, Centre for Gamete Cryopreservation, University of Padua; 3 Department of Environmental Medicine and Public Health, Institute of Hygiene, University of Padua Background and Aims: Inflammatory Bowel Disease (IBD) etiology is unknown although genetic, immunological, infectious, vascular and neural factors may
P092 AUTOLOGOUS STEM CELL TRANSPLANTATION IN MODERATE-SEVERE REFRACTORY CROHN' S DISEASE: THE MILAN EXPERIENCE WITHOUT CD 34+ CELL SELECTION A. Cassinotti 1, S. Ardizzone 1 , C. Annaloro 2 , F. Onida 2 , D. Trabattoni 3 , A. Della Volpe 2 , C. Vener 2 , G. Maconi 1 , S. Greco 1 , G. Lambertenghi Deliliers 2, M. Clerici 3 , G. Bianchi Porro 1 . 1 Department of Clinical Science, Gastroenterology Unit, L. Sacco University Hospital, Milan, Italy; 2 Bone Marrow Transplantation Centre, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy; 3 Chair of Immunology, University of Milan, Milan, Italy Background and aims: Autologous haematopoietic stem cell transplantation (aHSCT) with CD34+ cell selection has recently been used to treat refractory Crohn' s disease (CD), showing good safety and promising efficacy. We investigate the safety and efficacy of aHSCT without CD34+ cell selection in refractory CD. Patients and Methods: Four patients (3 males, 1 female; age 26-45 years) with active moderate-severe CD (median CDAI 316), refractory or intolerant to multiple drugs including infliximab, were enrolled. Unselected PBSCs were collected after mobilisation with CTX 1.5 g/m2 and G-CSF 10 g/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit ATG 2.5 mg/kg on days -4 to -2. Primary end point were toxicity and clinical remission (CDAI < 150) at 3 months. Secondary end point were endoscopic response (SES-CD) at 3 months and modulation of T reg (CD4/CD25/Foxp3) cells, a subset of lymphocyte with inhibitory actions, measured at baseline, 3 and 6 months. Results: No improvement or slight worsening was observed after mobilisation (median CDAI 335, range 258-404). At the third month, the primary end-point was reached in all patients, with a median CDAI of 85 (range 56-102) despite discontinuation of all medication, apart from antibiotics in two patients with perianal fistula. Endoscopic scores improved in 3/4 patients. No unexpected serious adverse events were observed, except for a new perianal abscess after mobilisation in one patient, idiopathic pericarditis in another and hemorrhagic cistitis by Staph aureus in an other patient, all quickly treated with conservative therapy. At 6 months CD4/CD25/Foxp3 cells were lesser in the unique patient that didn' t reach also endoscopic remission. Conclusion: Unselected CD34+ cells transplantation is safe overall and can induce remission in previous refractory patients. Interesting immunomodulatory effects are suggested. Further recruitment and long-term results are ongoing.
27 P093 RESTORATIVE PROCTOCOLECTOMY FOR ULCERATIVE COLITIS: IMPACT ON LIPID METABOLISM AND ON TISSUTAL AND SERUM FATTY ACIDS M. Scarpa 1 , G. Romanato 2 , E. Manzato 2 , C. Ruffolo 1 , R. Marin 2 , S. Basato 1 , S. Zannoni 2 , S. Zambon 2 , T. Filosa 1 , F. Pilon 1 , L. Polese 1 , I. Angriman 1 . 1 Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, University of Padova; 2 Clinica Medica I, Dipartimento di Scienze Mediche e Chirurgiche, University of Padova Objective: Even if intestinal absorption is not directly impaired ulcerative colitis (UC) deserves important metabolic implications. In fact, chronic inflammation and accelerated intestinal transit may significantly influence lipid metabolism. Restorative proctocolectomy (RPC) usually obtains the resolution of inflammatory process but the accelerated transit may persist The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids of UC patients after RPC. Method: Fifteen patients who underwent RPC for UC between December 2004 and April 2006 were enrolled. Disease activity, diet, inflammatory parameters, lipid profile and composition of fatty acids (FA) of serum phospholipids were assessed at RPC and at ileostomy closure. In 9 patients at RPC, and in 10 at the ileostomy closure, FA composition of phospholipids of subcutaneous adipose tissue were also evaluated. Fifteen sex-and-age matched healthy subjects were enrolled as controls. Data were expressed as median (range) and Wilcoxon paired- and Mann-Whitney U tests were used. Results: The median interval between RPC and ileostomy closure was 6 (29) months. In UC patients total cholesterol was significantly lower than in healthy subjects at RPC and at ileostomy closure. During that interval the inflammatory parameters improved as well as lipid profile (median HDLcholesterol: from 43 (19-65) to 56 (25-84) mg/dl, p<0.01; median LDLcholesterol: from 100 (26-160) to 52 (24-139) mg/dl, p=0.01). At ileostomy closure serum arachidonic acid and docosaesaenoic acid levels were increased compared to levels at RPC (p=0.04 and p=0.05, respectively), while serum oleic acid level was decreased (p=0.02). No significant alteration in serum n-3 FA precursors was observed in UC patients in the interval between RPC and ileostomy closure. On the contrary 22:6 n3 appeared to be lower in UC patients at ileostomy closure compared to healthy controls (p<0.01). No significant differences in the composition of FA of subcutaneous adipose tissue were observed between RPC and ileostomy closure. Conclusion: The increase of serum percentage of arachidonic acid after RCP might be explained by a lower utilization for inflammatory process The observed reduction of LDL cholesterol could be an index of malabsorption and was probably due to the persistency of an accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.
P094 CLINICAL, SURGICAL AND GENETIC RISK FACTORS FOR DEVELOPMENT OF POUCHITIS FOLLOWING IPAA FOR ULCERATIVE COLITIS M. Ferrante 1, S. Declerck 1 , T. Koopman 1 , M. Pierik 1 , P. Rutgeerts 1 , G. Van Assche 1 , A. D' Hoore 2 , F. Penninckx 2 , S. Vermeire 1 . 1 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2 Department of Abdominal Surgery, University Hospital Gasthuisberg, Leuven, Belgium Background & Aims: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The pathogenesis is unclear, although faecal stasis and bacterial overgrowth are judged important etiologic factors. We therefore investigated the role of microbial pattern recognition receptor genes in prediction of pouchitis after IPAA. Methods: A total of 132 (77 male) consecutive patients with IPAA for UC were studied. Median (interquartile range, IQR) age at surgery was 39.8 (31.6-47.8) years. Fourteen percent were active smokers at surgery, while 49% percent had never smoked. Fifty-two percent had extra-intestinal manifestations (EIM), 73% had extensive colitis, 6% had backwash ileitis. Surgery was performed in 1, 2 or 3 stages in, respectively, 16%, 69% and 15% and laparoscopic assisted in 47%. All patients were genotyped by PCR-RFLP for 56 non-synonymous polymorphisms in Toll Like Receptors (TLRs) 1-10, 3 common CARD15 mutations, TNF -G308A, CD14 —C260T and a variable number tandem repeat in intron 2 of IL1-RA. Diagnosis of pouchitis was based on clinical, endoscopic and histological criteria. Pouchitis was defined acute relapsing if patient had 3 or more acute episodes of pouchitis; and chronic if symptoms lasted for more than 4 weeks, despite a full dose of standard therapy. Results: With a median (IQR) follow-up of 6.5 (3.3-9.8) years, 64 patients (48%) developed pouchitis (24 acute, 11 relapsing and 29 chronic). One patient needed pouchectomy for pouch necrosis. Median (IQR) duration between restoration of transit and first pouchitis episode was 12 (5-28) months. In multivariate analysis young age at surgery (36.0 vs. 42.5 years, Odds ratio (OR) 1.04, 95% CI 1.01-1.08, p=0.015), presence of EIM (59% vs. 38%, OR 2.25, 95% CI 1.21-5.30, p=0.014) and presence of a T allele in TLR1 S87I (57%
28 vs. 41%, OR 2.13, 95% CI 1.02-4.45, p=0.044) were independently associated with pouchitis, and with faster onset of pouchitis (Kaplan-Meier respectively, p=0.017, p=0.001 and p=0.066). Chronic pouchitis was inversely associated with disease duration before surgery (3.6 vs. 7.8 years, OR 0.91, 95% CI 0.830.99, p=0.036) and presence of a CD14 -260C allele (36% vs. 68%, OR 0.23, 95% CI 0.06-0.83, p=0.025). Discussion: Young age at surgery, presence of EIM and TLR1 S87I were independently associated with early development of pouchitis in UC. Short duration of disease and presence of CD14 -260C allele were associated with chronic pouchitis. Both TLR1 and CD14 are co-factors of the lipopolysaccharide receptor complex and support the hypothesis that bacterial recognition is important in the onset of this complication after IPAA.
P095 LONG-TERM SAFETY OF AZATHIOPRINE TREATMENT IN INFLAMMATORY BOWEL DISEASE: RESULTS FROM A SINGLE REFERRAL CENTER K. Katsanos 1,2 , M. Ferrante 1, H. Fidder 1 , L. Henckaerts 1, D. Christodoulou 2 , G. Van Assche 1 , E. Tsianos 2, S. Vermeire 1 , P. Rutgeerts 1 . 1 Department of Gastroenterology, University of Leuven Hospitals, Leuven, Belgium; 2 1st Division of Internal Medicine & Hepato-Gastroenterology Unit, University Hospital of Ioannina, Greece Background: There is conflicting data regarding long-term safety including risk of malignancy in inflammatory bowel disease (IBD) patients receiving azathioprine (AZA). Aim: To describe the long-term safety including the prevalence of malignancies in a large cohort of IBD patients treated with AZA in a single referral center. Patients and Methods: Retrospective data collection from a computerized database of 1815 IBD patients (1355 Crohn' s [CD], 447 ulcerative colitis [UC], 13 indeterminate colitis [IC]). All patients who previously received or were currently taking AZA were identified and reviewed for occurrence and type of malignancies. Results: We identified 729 IBD patients previously or currently on AZA (555 CD, 169 UC, 5 IC). Median disease duration was 12 years (interquartile range [IQR] 7-19 years) and follow up on AZA/6-MP was (median, IQR) 7.1 (4.49.7) years. Combination therapy with Infliximab (IFX) was administered in 232 patients (208 CD). Before and during AZA segmental bowel resection was performed in 190 (26.2%) patients and total colectomy in 74(10.2%). A total of 15 patients [2%] (12 CD, 3UC/12 females, 3 males) were diagnosed with 17 cancers, all extra-intestinal but no lymphoma. Thirteen patients were on concomitant IFX. There was no significant difference in age, gender, duration of disease, and duration of AZA therapy between AZA-cancer and AZA non-cancer patients (data not shown). In the whole AZA cohort mortality rate was 0.82% (6/729 patients) while all AZA-cancer patients were alive on latest follow up. We identified 88/729 (12%) patients with AZA-related bone marrow toxicity (BMT) necessitating dose adjustment or interruption of therapy. Infections were diagnosed in 27 BMT patients (30%), 8 of them were severe and 4/8 were of viral origin. Conclusions: In this large single center cohort of 729 IBD patients treated with AZA, the mortality rate was 0.82% and prevalence of cancer was 2%, all extra-intestinal. Duration of therapy, disease duration, age, presence of BMT were not associated with a higher cancer risk. BMT was associated with infections in a third of patients and half of severe infections were viral.
P096 LIPID AND PHOSPHOLIPID PROFILE SIX MONTHS AFTER ILEO-COLONIC RESECTION FOR CROHN' S DISEASE G. Romanato 1 , M. Scarpa 2 , C. Ruffolo 2 , R. Marin 1 , S. Zannoni 1 , S. Zambon 1 , S. Basato 2 , T. Filosa 2 , F. Pilon 2 , I. Angriman 2 , E. Manzato 1 . 1 Clinica Medica I, Dipartimento di Scienze Mediche e Chirurgiche, University of Padova; 2 Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, University of Padova Objective: The patients affected by Crohn' s disease (CD) present often with a malnutrition status, that may persists even after the acute phase of disease. The aim of this prospective study was to evaluate which effect may have surgical induced remission on the lipid and phospholipids profile. Method: Thirty-seven patients, who underwent ileo-colonic resection for CD between December 2004 and April 2006, were enrolled in this prospective study. Anthropometric parameters, disease activity, diet, inflammatory parameters, lipid profile and serum phospholipids fatty acids (FA) composition were assessed at ileo-colonic resection and after 6 months. Data were expressed as mean (range) and t-test for paired data and Spearman correlations between percent variation (delta%) were used. Result: The mean interval between resection and control was 6 (4-9) months. During this interval CRP serum levels decreased, even if not significantly,
Poster Presentations and albumin levels were significantly increased (38.0 vs 43.1g/l, p=0.015). In lipid profile the only modification was a significant increase of HDL cholesterol (from 48±19 to 57±19 mg/dl, p<0.01). Serum arachidonic acid (20:4 n6) and adrenic acid (22:4 n6) decreased significantly after 6 months of interval. A significant correlation between the delta% of weight and eicosanoic (20:1 n9) (r=-0.93, p= p<0.01) and eicosapentaenoic acid (EPA) (20:5 n3) (r=0.82, p=0.02) was observed. The delta% of CRP directly correlated with delta% of oleic acid (18:1 n9) (r=0.82, p=0.02) and with those of palmitoleic acid (16:1 n7) (r=0.82, p=0.02), and inversely with those of stearic acid (18:0) (r=-0.86, p=0.01). Conclusion: The restoration of the intestinal physiological properties after ileo-colonic resection is probably the cause of HDL cholesterol increase since the HDL proteins are produced in the intestine. The serum fatty acid modifications, that were observed after the 6 months follow up, could be attributed to dietary modifications and to modification of the activities of the liver enzymes that regulates fatty acid metabolism (i.e. elongase and desaturase). In fact, the activity of these enzymes is strictly related to the disease activity.
P097 NATURAL HISTORY OF CYTOMEGALOVIRUS INFECTION IN A COHORT OF PATIENTS DIAGNOSED WITH MODERATE-SEVERE ULCERATIVE COLITIS V. Criscuoli 1 , M.R. Rizzuto 2 , E. Gallo 2 , M.C. Renda 3 , A. Orlando 1 , L. Montalbano 4 , M. Cottone 1 . 1 Medicine, Pneumology and Physiology of Human Nutrition Department. "V.Cervello" Hospital Palermo; 2 Institute of Pathology, "V.Cervello" Hospital Palermo; 3 Ematology II Division, "V.Cervello" Hospital Palermo; 4 Gastroenterology Division, "V.Cervello" Hospital Palermo Aim of the study: The relationship between Cytomegalovirus (CMV) infection and Inflammatory Bowel Disease (IBD) is well-known since many years. Prevalence data reported are different on the basis of diagnostic methods used. The aim of this study is to evaluate the natural history of CMV infection on a series of 25 patients (pts) admitted to our department from 1999 to 2006 for a reactivation of ulcerative colitis, in which the histopathological search for CMV resulted positive. Patients and Methods: 110 consecutive patients with moderate-severe ulcerative colitis flare-up ( according to the Truelove criteria) were admitted to the Medicine Department of V.Cervello Hospital in Palermo. On admission a CMV search was conducted performing an haematoxylin and eosin (H&E) stain on rectal biopsies searching for a tipical cytomegalic cell and inclusion bodies and Immunoistochemical (ICH) assay to detect viral protein. Among 110 patients, 25 (9 women and 16 men) resulted positive for CMV infection (both H&E and ICH). After recovery the patients were followed -up clinically every three months and histologically every two years by multiple biopsies obtained during colonoscopic assessment. The specimens collected (in all 260) were examined with E&O, ICH and tissue nested PCR for CMV DNA using primer pairs specific for Cytomegalovirus. Results: The median clinical and endoscopic follow-up was 40 months (9-72). Among 25 pts five were lost at follow-up (one died due to a cause not related to ulcerative colitis, four were operated on for severe disease). Among the 20 pts with complete follow-up, 5 (20%) pts were found positive for CMV DNA in intestinal specimens. Eight (40%) experienced at least one moderate-severe flare-up of colitis. In 3 out of 8, CMV DNA was detected by PCR in intestinal tissue (37.5%). Among the 12 patients who maintained clinical remission CMV DNA was detected in two (16%). The number of cases was too small to detect a statistical significance. Two out of 3 patients positive for CMV genome that experienced a colitis attack and one out of two patients positive for CMV in remission were maintained with immunosuppressant. Conclusions: Our preliminary results suggest that the CMV may remain in the colon despite remission. There was a slight more higher relapse in patients with detected CMV by nested PCR in intestinal tissue samples after recovery of a colitis. Prospective and controlled studies in large cohorts of IBD patients are needed to confirm this observation.
P098 FERTILITY AND SEXUAL ACTIVITY DISORDERS IN MALE PATIENTS WITH INFLAMMATORY BOWEL DISEASE D. Checchin 1 , A. Garolla 2 , M. Lisiero 3 , M. Martinato 1 , R. D' Incà 1 , C. Foresta 2, G.C. Sturniolo 1 . 1 Department of Surgical and Gastroenterological Sciences, University of Padua; 2 Department of Hystology, Microbiology and Medical Biothecnologies, Centre for Gamete Cryopreservation, University of Padua; 3 Department of Environmental Medicine and Public Health, Institute of Hygiene, University of Padua Background and Aims: Inflammatory Bowel Disease (IBD) etiology is unknown although genetic, immunological, infectious, vascular and neural factors may