- Email: [email protected]
P.1.29: A SUSTAINED VIROLOGICAL RESPONSE TO INTERFERON PREVENTS INSULIN RESISTANCE IN CHRONIC HEPATITIS C PATIENTS
Abstracts of the XVII National Congress of Digestive Diseases / Digestive and Liver Disease 43S (2011) S115–S264 pathologist blindly reported the Marsh histological grade for the diagnosis of CD of the bulb and descending duodenum. Results: Were 46 F and 27 M. Mean Hb was of 12.1±2.1 mg/dl; mean RBC: 4.3±1.2 mln/lt; MCV: 79.5±11.1 fL. Diarrhea was encountered in 56.2% of the patients; bloating in 76.2%; weight loss in 30.1%; delayed growth in 26%; loss of Kierkering’s fold: 36.9%; scalloping: 58.9%; bubbly mucosa: 30.1%; diabetes: 10.4%. Hp (+) was encountered on 17.8% (13/73) of the patients. The diagnosis of CD was histologically confirmed in 97.3% (71/73) of the cases; 2 patients were Marsh 0 in bulb and duodenum. Of the 71 celiac patients the diagnosis of CD was histologically confirmed in 91.5% (65/71) of biopsies obtained from the descending duodenum and in all 71 obtained from the bulb. In 53 patients (74.6%), histology was the same in the bulb and duodenum; in 17 (23.9%) cases the grade of atrophy was higher in the bulb than in the decending duodenum and 6 (8.5%) had positive bulb histology for CD but negative duodenal findings. Two patients (2.8%) had a higher histological grade in the duodenum than in the bulb. The diagnostic gain with bulbar biopsies was 8.5%. Conclusions: We suggest examining four biopsies from the duodenal bulb and four from the descending duodenum to improve diagnostic accuracy for CD.
P.1.27 THE REGULATORY CD163-POSITIVE MACROPHAGES INFILTRATE MASSIVELY THE INFLAMED GUT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES E. Franzè ∗ , C. Stolfi, F. Caprioli, F. Zorzi, I. Monteleone, S. Carli, L. Biancone, F. Pallone, G. Monteleone Università Tor Vergata, Roma, Italy Background and aim: The hemoglobin scavenger receptor, CD163, is a marker classically expressed by anti-inflammatory macrophages, and CD163positive macrophages are supposed to play a key role in the resolution of acute inflammation and tissue wound healing. Therefore, defects in the recruitment or activity of CD163-expressing cells to inflamed tissues might contribute to sustain and amplify inflammatory processes. Since inflammatory bowel disease (IBD)-associated immune response has been recently associated with a diminished mucosal infiltration of regulatory macrophages, we here characterized the tissue and blood distribution of CD163-positive cells in patients with Ulcerative colitis (UC) and patients with Crohn’s disease (CD). Material and methods: Paired biopsies were taken from inflamed and uninflamed mucosa of patients with UC and patients with CD. Normal controls included samples taken from patients with irritable bowel syndrome or subjects undergoing colonoscopy for colon cancer screening. CD163 expression was examined by immunohistochemistry and real-time PCR. Additionally, peripheral blood mononuclear cells (PBMC) were obtained from IBD patients and controls and analyzed for CD163, CD14, and CD16 expression by flow-cytometry. Results: A significant increase in CD163 RNA expression was seen in inflamed mucosal samples of patients with IBD as compared to uninvolved areas of the same patients and normal controls. Immunohistochemical analysis confirmed the more pronounced accumulation of CD163-expressing cells in IBD, mostly around deep ulcers. CD163-positive cells were also seen around and inside blood vessels, thus suggesting that these cells are probably recruited from the systemic circulation. Indeed, FACS analysis of freshly isolated PBMC showed that the fraction of CD163-positive cells was increased in IBD patients as compared to controls, and that more than 90% of those cells expressed CD14. By contrast, less than 10% of blood CD163-positive cells expressed CD16, a marker typically expressed by inflammatory monocytes. Conclusions: Data indicate that the regulatory CD163-positive macrophages are abundant in the inflamed tissue of IBD patients, where they probably contribute to counter-regulate the ongoing inflammation.
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P.1.28 ANTI-TNF THERAPY REDUCES CIRCULATING REACTIVE OXYGEN SPECIES AND RESTORES SERUM ANTIOXIDANT POTENTIAL IN INFLAMMATORY BOWEL DISEASE PATIENTS L. Pastorelli ∗ ,1 , C. Testa 2 , C. De Salvo 3 , L. Spina 2 , G. Tontini 2 , N. Munizio 2 , M. Vecchi 1 1 Universitá degli Studi di Milano, Milano, Italy; 2 Irccs Policlinico San Donato, San Donato Milanese, Italy; 3 Universitá di Bologna, Bologna, Italy
Background and aim: Circulating reactive oxygen species (ROS) are increased during inflammatory states. ROS production can cause direct tissue damage, altering biomolecules, such as lipids, proteins and nucleic acids, and activate inflammatory pathways. ROS production plays a role in eliciting the inflammatory cascade and mucosal injury characterizing Inflammatory Bowel Diseases (IBD); in fact IBD patients display elevated serum and tissue ROS and reduced levels of antioxidant enzymes, and free radical scavenger compounds have been shown to be effective in ameliorating intestinal inflammation in experimental models of colitis. Accordingly, TNF, a key inflammatory mediator in IBD, increases ROS production. Anti-TNF monoclonal antibody therapy is indeed effective in inducing remission or reducing disease activity in IBD; the blockade of TNF acts at different levels, which are yet to be fully characterized. Aim of the present study is to evaluate if anti-TNF therapy may modify oxidoreductive state in IBD patients. Material and methods: 42 sera were collected from 14 IBD patients (8 CD, 6 UC), before each of the first 3 Infliximab (IFX) infusions of the therapeutic regimen. Serum ROS were evaluated using the d-ROM test, spectrophotometric test based on the measurement of hydroperoxide generated by ROS; biological antioxidant potential (BAP), as a measure of plasmatic antioxidant barrier, was determined using the BAP test, colorimetric test assessing the plasmatic antioxidant power. Statistical analysis was performed by means of paired Student’s t test. Results: Serum ROS levels were markedly reduced throughout IFX therapy, as observed comparing the first to the third infusion (370.49±135.58 vs. 294.46±96.94 Ucarr; p<0.005); BAP was transiently increased after the first infusion (4251.63±508.36 vs. 4950.93±460.35 mmol/l; p<0.0005), but was restored to the original level before the third infusion. Conclusions: Taken together, our data show that anti-TNFa therapy significantly modifies serum oxidative stress in IBD patients, reducing ROS production and increasing antioxidant potential, suggesting another possible mechanism through which IFX exerts its therapeutic effect.
P.1.29 A SUSTAINED VIROLOGICAL RESPONSE TO INTERFERON PREVENTS INSULIN RESISTANCE IN CHRONIC HEPATITIS C PATIENTS G.M. Prati ∗ ,1 , A. Aghemo 1 , M. Rumi 2 , R. Soffredini 1 , R. D’Ambrosio 1 , S. De Nicola 1 , E. De Gasperi 1 , L. Olgiati 1 , M. Colombo 1 1 Fondazione 2 Ospedale
Irccs Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; San Giuseppe, Università degli Studi di Milano, Milan, Italy
Background and aim: It is well established that insulin resistance (IR) influences both natural history and response to pegylated interferon (PegIFN)/ribavirin (Rbv) therapy in patients with hepatitis C virus (HCV) infection. Less clear is whether treatment related HCV eradication influences IR. To assess this we analyzed serum markers of IR with respect to the outcome of a randomized clinical study of Peg-IFN/Rbv therapy in chronic hepatitis C patients (MIST study). Material and methods: Three hundred and ninety nine non diabetic patients, who received Peg-IFN alfa2-a or alfa2-b/Rbv, had serum insulin levels measured by fluoroimmunometric assays. IR, defined as homeostasis model assessment (HOMA) > 2, was assessed at baseline and 18 months after treatment completion. Liver fibrosis (S) was quantified by Ishak and steatosis was assigned as mild (< 33% liver cells) and moderate-severe (>33%). Results: IR was detected in 48/399 patients (12%) and predicted by body weight (OR 2.42; 95%CI, 1.1–5.3; p=0.03), HCV load <0.6×106 IU/l (OR 2.57; 95%CI, 1.3-5.1; p=0.006), S ≥4 (OR 2.44; 95%CI, 1.2-4.9; p=0.01),
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and moderate-severe steatosis (OR 2.1; 95%CI, 1.1-4.1; p=0.03). SVR rates were not related to HOMA in the overall population [63% (220/351) vs 60% (29/48), p=0.75], nor in subgroup analysis by virus genotype [genotype 1: 43% (61/143) for ≤ 2 HOMA vs 53% (9/17) for > 2 HOMA (p=0.45); genotype 2 and 3: 83% (143/173) vs 80% (20/25), p=0.78, respectively]. In SVR patients, baseline and follow up HOMA values were similar (1.12±0.82 vs 1.17±1.1, p=0.25). Conversely, nonresponders had increased HOMA values trough 18 months follow up (from 1.17±0.7 to 1.49±1.3, p=0.007); IR de-novo occurred more frequently in non-SVR than in SVR patients [24% (25/106) vs 8% (16/198), p=0.0003]. Conclusions: While the outcome of Peg-IFN/Rbv therapy is not influenced by IR, the latter is prevented once SVR is achieved.
P.1.30 SECONDARY CANCERS IN PATIENTS WITH INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS (IPMN): PRELIMINARY RESULTS OF A PROSPECTIVE MULTICENTRE ITALIAN STUDY A. Larghi ∗ ,1 , G. Capurso 2 , S. Boccia 3 , R. Salvia 4 , M. Del Chiaro 5 , M. Piciucchi 2 , A. Carnuccio 1 , S. Carrara 6 , R. Manta 7 , C. Fabbri 8 , E. De Feo 3 , G. Leonardi 9 , P.G. Arcidiacono 6 , U. Boggi 5 , G. Delle Fave 2 , G. Costamagna 1 , C. Bassi 4 1 Digestive
Endoscopy Unit, Catholic University, Rome, Rome, Italy; and Liver Disease Unit, University La Sapienza,ii Medical School, Rome, Italy; 3 Epidemiology, Catholic University, Rome, Rome, Italy; 4 Surgery, University of Verona, Verona, Italy; 5 Surgey, University of Pisa, Pisa, Italy; 6 Division of Gastroenterology & Gastrointestinal Endoscopy, San Raffaele Scientific Institute, Milano, Italy; 7 Gastroenterology, Nuovo Ospedale S. Agostino, Modena, Modena, Italy; 8 Gastroenterology, Bellaria-Maggiore Hospital, Bellaria, Italy; 9 Gastroenterology, University of Pisa, Pisa, Italy 2 Digestive
Background and aim: Intraductal papillary mucinous neoplasms (IPMN) are associated with an increased risk to develop a coexistent ductal adenocarcinoma (PDAC). There is also increasing evidence that patients affected by IPMNs could be at higher risk of extrapancreatic synchronous or metachronous secondary cancers (SC), with highest rates for colorectal and gastric cancer. However, the existing studies, mainly conducted in Asia, are somehow inconclusive regarding the site, incidence and prevalence of SC in IPMNs. We aimed at evaluating the incidence of SC in IPMNs, and possible risk factors for their occurrence. Material and methods: Cohort of consecutive patients with diagnosis of IPMN. SC defined as a different tumor, diagnosed histologically either before, sincronously or after IPMN diagnosis. Data on sex, age at diagnosis of IPMN, medical therapy and potential risk factors for cancer recorded and differences between subgroups evaluated by appropriate statistics. Results: 78/274 (28.5%) patients with IPMN had at least one SC (57 before, 19 synchronous, 2 after the diagnosis of IPMN). Most frequent SCs were: mammary=12 colorectal=10, PDAC=4, renal=5, prostate=7, GIST=3 pancreatic endocrine tumour=2). There were no differences in the rate of SC between males and female, no relation with age at diagnosis of IPMN, nor with IPMN type (BD vs MD). IPMN patients with a SC were more likely to have a 1st degree family history of any cancer as compared to IPMN patients without SC (60.5% vs 45.8% p=0.041). In the group of SC patients we observed higher rates of heavy (= 20 pack/year) smokers (36.4% vs 25.25) and alcohol users (50% vs 38.3%), but these differences were not statistically significant. Conclusions: In this cohort of patients with IPMN, the incidence of SC was higher than expected in the Italian population, and the high incidences of mammary (4.3%) colorectal (3.7%) and pancreatic (1.5%) adenocarcinoma, possibly suggest common genetic susceptibility. An association with GIST and pancreatic endocrine tumour was also noted. Most SC were diagnosed before or at the time of the diagnosis of IPMN. Alchool, Smoking and 1st degree FH of cancer may be associated with an increased risk of SC.
P.1.31 VARIANTS OF THE OBESITY-ASSOCIATED FTO GENE AND COLORECTAL CANCER RISK IN ITALY E. Tarabra 1 , G. Actis ∗ ,2 , E. Borghesio 2 , G. Tappero 2 , L. Framarin 2 , M. Fadda 3 , P. De Paolis 4 , A. Comandone 5 , R. Coda 6 , F. Rosina 2 1 Center
for Predictive Medicine, Presidio Sanitario Gradenigo, Torino, Italy; & Epatologia - Presidio Sanitario Gradenigo, Torino, Italy; 3 Dipartimento di Nutrizione Clinica - Ospedale Molinette, Torino, Italy; 4 Divisione di Chirurgia- Presidio Sanitario Gradenigo, Torino, Italy; 5 Divisione di Oncologia - Presidio Sanitario Gradenigo, Torino, Italy; 6 Istopatologia - Presidio Sanitario Gradenigo, Torino, Italy 2 Gastroenterologia
Background and aim: Second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be associated with obesity. Aim of the study was to establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma. Material and methods: 622 subjects who underwent colonoscopy from July 2001 to July 2008 were enrolled in the study and divided in 3 groups according to endoscopic, histologic and clinical findings: CRC (203 pts, M/F 116/87, mean age 65±11 yrs), colorectal adenoma (112 pts, M/F 61/51, mean age 62±13 yrs), healthy controls (307 pts, M/F 151/156, mean age 58±13 yrs). Rs9939609 was genotyped by real-time PCR. Results: Genotype frequencies did not deviate from the Hardy-Weinberg predictions. The FTO rs9939609 A allele frequency was 0.448, 0.449, and 0.411 for the controls, CRC and polyps patients respectively. In the healthy subjects, the FTO variant associated to the risk of obesity defined by the presence of the A allele (AA + AT genotypes) - was 69.38% (213/307); the FTO variant associated to low-risk of obesity - defined by TT genotype - was 30.62% (94/307). The proportion of individuals bearing the risk allele (AA or AT genotypes) was 72% (146/203) and 62% (69/112) in CRC and polyp patients. Compared to controls the obesity-associated FTO variant (AA genotype) had no significant effect on the risk for either CRC (OR=1.498; CI 95%=0.9872.276; p= 0.063) or colorectal adenomas (OR=0.708; CI 95%=0.451-1.112; p=0.158). In both CRC and colorectal polyps there were no differences on genotype frequency between age at diagnosis, genders and disease site. Conclusions: The obesity-linked FTO variants do not seem to play a significant role in modulating the colorectal cancer risk in the Italian population. However, highlighting a borderline significance, statistical elaboration of the data leaves a door open to interpretation. The study was supported by Regione Piemonte Italy – Direzione Sanità – Ricerca Sanitaria Finalizzata – Protocollo n. 2472/DA2001.
P.1.32 APPROPRIATENESS OF SURVEILLANCE COLONOSCOPY AFTER ADENOMA REMOVAL IN COLORECTAL CANCER (CRC) SCREENING PROGRAMME F. Monica ∗ ,1 , C. Fedato 2 , M. Zorzi 2 , C.S.G. Veneto Endoscopic 2 1 Ospedale
S. Bassiano, Bassano Del Grappa (VI), Italy; 2 Registro Tumori Del Veneto, Padova, Italy Background and aim: CRC screening programmes based on fecal occult blood test (FOBT) and colonoscopy (CS) detect an high number of individuals with adenomas, but little is known about appropriateness in these patients (pts). Aim of this study is to evaluate the appropriateness of timing of surveillance CS in CRC screening programmes in Veneto Region. Material and methods: Data collected in 2009 from 12 screening programmes in Veneto were retrospectively analyzed using the regional database. In FOBT+ve subjects undergoing CS, endoscopic and istopathological data were recorded and indication for surveillance interval, advised by endo-
P.1.27 THE REGULATORY CD163-POSITIVE MACROPHAGES INFILTRATE MASSIVELY THE INFLAMED GUT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES E. Franzè ∗ , C. Stolfi, F. Caprioli, F. Zorzi, I. Monteleone, S. Carli, L. Biancone, F. Pallone, G. Monteleone Università Tor Vergata, Roma, Italy Background and aim: The hemoglobin scavenger receptor, CD163, is a marker classically expressed by anti-inflammatory macrophages, and CD163positive macrophages are supposed to play a key role in the resolution of acute inflammation and tissue wound healing. Therefore, defects in the recruitment or activity of CD163-expressing cells to inflamed tissues might contribute to sustain and amplify inflammatory processes. Since inflammatory bowel disease (IBD)-associated immune response has been recently associated with a diminished mucosal infiltration of regulatory macrophages, we here characterized the tissue and blood distribution of CD163-positive cells in patients with Ulcerative colitis (UC) and patients with Crohn’s disease (CD). Material and methods: Paired biopsies were taken from inflamed and uninflamed mucosa of patients with UC and patients with CD. Normal controls included samples taken from patients with irritable bowel syndrome or subjects undergoing colonoscopy for colon cancer screening. CD163 expression was examined by immunohistochemistry and real-time PCR. Additionally, peripheral blood mononuclear cells (PBMC) were obtained from IBD patients and controls and analyzed for CD163, CD14, and CD16 expression by flow-cytometry. Results: A significant increase in CD163 RNA expression was seen in inflamed mucosal samples of patients with IBD as compared to uninvolved areas of the same patients and normal controls. Immunohistochemical analysis confirmed the more pronounced accumulation of CD163-expressing cells in IBD, mostly around deep ulcers. CD163-positive cells were also seen around and inside blood vessels, thus suggesting that these cells are probably recruited from the systemic circulation. Indeed, FACS analysis of freshly isolated PBMC showed that the fraction of CD163-positive cells was increased in IBD patients as compared to controls, and that more than 90% of those cells expressed CD14. By contrast, less than 10% of blood CD163-positive cells expressed CD16, a marker typically expressed by inflammatory monocytes. Conclusions: Data indicate that the regulatory CD163-positive macrophages are abundant in the inflamed tissue of IBD patients, where they probably contribute to counter-regulate the ongoing inflammation.
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P.1.28 ANTI-TNF THERAPY REDUCES CIRCULATING REACTIVE OXYGEN SPECIES AND RESTORES SERUM ANTIOXIDANT POTENTIAL IN INFLAMMATORY BOWEL DISEASE PATIENTS L. Pastorelli ∗ ,1 , C. Testa 2 , C. De Salvo 3 , L. Spina 2 , G. Tontini 2 , N. Munizio 2 , M. Vecchi 1 1 Universitá degli Studi di Milano, Milano, Italy; 2 Irccs Policlinico San Donato, San Donato Milanese, Italy; 3 Universitá di Bologna, Bologna, Italy
Background and aim: Circulating reactive oxygen species (ROS) are increased during inflammatory states. ROS production can cause direct tissue damage, altering biomolecules, such as lipids, proteins and nucleic acids, and activate inflammatory pathways. ROS production plays a role in eliciting the inflammatory cascade and mucosal injury characterizing Inflammatory Bowel Diseases (IBD); in fact IBD patients display elevated serum and tissue ROS and reduced levels of antioxidant enzymes, and free radical scavenger compounds have been shown to be effective in ameliorating intestinal inflammation in experimental models of colitis. Accordingly, TNF, a key inflammatory mediator in IBD, increases ROS production. Anti-TNF monoclonal antibody therapy is indeed effective in inducing remission or reducing disease activity in IBD; the blockade of TNF acts at different levels, which are yet to be fully characterized. Aim of the present study is to evaluate if anti-TNF therapy may modify oxidoreductive state in IBD patients. Material and methods: 42 sera were collected from 14 IBD patients (8 CD, 6 UC), before each of the first 3 Infliximab (IFX) infusions of the therapeutic regimen. Serum ROS were evaluated using the d-ROM test, spectrophotometric test based on the measurement of hydroperoxide generated by ROS; biological antioxidant potential (BAP), as a measure of plasmatic antioxidant barrier, was determined using the BAP test, colorimetric test assessing the plasmatic antioxidant power. Statistical analysis was performed by means of paired Student’s t test. Results: Serum ROS levels were markedly reduced throughout IFX therapy, as observed comparing the first to the third infusion (370.49±135.58 vs. 294.46±96.94 Ucarr; p<0.005); BAP was transiently increased after the first infusion (4251.63±508.36 vs. 4950.93±460.35 mmol/l; p<0.0005), but was restored to the original level before the third infusion. Conclusions: Taken together, our data show that anti-TNFa therapy significantly modifies serum oxidative stress in IBD patients, reducing ROS production and increasing antioxidant potential, suggesting another possible mechanism through which IFX exerts its therapeutic effect.
P.1.29 A SUSTAINED VIROLOGICAL RESPONSE TO INTERFERON PREVENTS INSULIN RESISTANCE IN CHRONIC HEPATITIS C PATIENTS G.M. Prati ∗ ,1 , A. Aghemo 1 , M. Rumi 2 , R. Soffredini 1 , R. D’Ambrosio 1 , S. De Nicola 1 , E. De Gasperi 1 , L. Olgiati 1 , M. Colombo 1 1 Fondazione 2 Ospedale
Irccs Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; San Giuseppe, Università degli Studi di Milano, Milan, Italy
Background and aim: It is well established that insulin resistance (IR) influences both natural history and response to pegylated interferon (PegIFN)/ribavirin (Rbv) therapy in patients with hepatitis C virus (HCV) infection. Less clear is whether treatment related HCV eradication influences IR. To assess this we analyzed serum markers of IR with respect to the outcome of a randomized clinical study of Peg-IFN/Rbv therapy in chronic hepatitis C patients (MIST study). Material and methods: Three hundred and ninety nine non diabetic patients, who received Peg-IFN alfa2-a or alfa2-b/Rbv, had serum insulin levels measured by fluoroimmunometric assays. IR, defined as homeostasis model assessment (HOMA) > 2, was assessed at baseline and 18 months after treatment completion. Liver fibrosis (S) was quantified by Ishak and steatosis was assigned as mild (< 33% liver cells) and moderate-severe (>33%). Results: IR was detected in 48/399 patients (12%) and predicted by body weight (OR 2.42; 95%CI, 1.1–5.3; p=0.03), HCV load <0.6×106 IU/l (OR 2.57; 95%CI, 1.3-5.1; p=0.006), S ≥4 (OR 2.44; 95%CI, 1.2-4.9; p=0.01),
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and moderate-severe steatosis (OR 2.1; 95%CI, 1.1-4.1; p=0.03). SVR rates were not related to HOMA in the overall population [63% (220/351) vs 60% (29/48), p=0.75], nor in subgroup analysis by virus genotype [genotype 1: 43% (61/143) for ≤ 2 HOMA vs 53% (9/17) for > 2 HOMA (p=0.45); genotype 2 and 3: 83% (143/173) vs 80% (20/25), p=0.78, respectively]. In SVR patients, baseline and follow up HOMA values were similar (1.12±0.82 vs 1.17±1.1, p=0.25). Conversely, nonresponders had increased HOMA values trough 18 months follow up (from 1.17±0.7 to 1.49±1.3, p=0.007); IR de-novo occurred more frequently in non-SVR than in SVR patients [24% (25/106) vs 8% (16/198), p=0.0003]. Conclusions: While the outcome of Peg-IFN/Rbv therapy is not influenced by IR, the latter is prevented once SVR is achieved.
P.1.30 SECONDARY CANCERS IN PATIENTS WITH INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS (IPMN): PRELIMINARY RESULTS OF A PROSPECTIVE MULTICENTRE ITALIAN STUDY A. Larghi ∗ ,1 , G. Capurso 2 , S. Boccia 3 , R. Salvia 4 , M. Del Chiaro 5 , M. Piciucchi 2 , A. Carnuccio 1 , S. Carrara 6 , R. Manta 7 , C. Fabbri 8 , E. De Feo 3 , G. Leonardi 9 , P.G. Arcidiacono 6 , U. Boggi 5 , G. Delle Fave 2 , G. Costamagna 1 , C. Bassi 4 1 Digestive
Endoscopy Unit, Catholic University, Rome, Rome, Italy; and Liver Disease Unit, University La Sapienza,ii Medical School, Rome, Italy; 3 Epidemiology, Catholic University, Rome, Rome, Italy; 4 Surgery, University of Verona, Verona, Italy; 5 Surgey, University of Pisa, Pisa, Italy; 6 Division of Gastroenterology & Gastrointestinal Endoscopy, San Raffaele Scientific Institute, Milano, Italy; 7 Gastroenterology, Nuovo Ospedale S. Agostino, Modena, Modena, Italy; 8 Gastroenterology, Bellaria-Maggiore Hospital, Bellaria, Italy; 9 Gastroenterology, University of Pisa, Pisa, Italy 2 Digestive
Background and aim: Intraductal papillary mucinous neoplasms (IPMN) are associated with an increased risk to develop a coexistent ductal adenocarcinoma (PDAC). There is also increasing evidence that patients affected by IPMNs could be at higher risk of extrapancreatic synchronous or metachronous secondary cancers (SC), with highest rates for colorectal and gastric cancer. However, the existing studies, mainly conducted in Asia, are somehow inconclusive regarding the site, incidence and prevalence of SC in IPMNs. We aimed at evaluating the incidence of SC in IPMNs, and possible risk factors for their occurrence. Material and methods: Cohort of consecutive patients with diagnosis of IPMN. SC defined as a different tumor, diagnosed histologically either before, sincronously or after IPMN diagnosis. Data on sex, age at diagnosis of IPMN, medical therapy and potential risk factors for cancer recorded and differences between subgroups evaluated by appropriate statistics. Results: 78/274 (28.5%) patients with IPMN had at least one SC (57 before, 19 synchronous, 2 after the diagnosis of IPMN). Most frequent SCs were: mammary=12 colorectal=10, PDAC=4, renal=5, prostate=7, GIST=3 pancreatic endocrine tumour=2). There were no differences in the rate of SC between males and female, no relation with age at diagnosis of IPMN, nor with IPMN type (BD vs MD). IPMN patients with a SC were more likely to have a 1st degree family history of any cancer as compared to IPMN patients without SC (60.5% vs 45.8% p=0.041). In the group of SC patients we observed higher rates of heavy (= 20 pack/year) smokers (36.4% vs 25.25) and alcohol users (50% vs 38.3%), but these differences were not statistically significant. Conclusions: In this cohort of patients with IPMN, the incidence of SC was higher than expected in the Italian population, and the high incidences of mammary (4.3%) colorectal (3.7%) and pancreatic (1.5%) adenocarcinoma, possibly suggest common genetic susceptibility. An association with GIST and pancreatic endocrine tumour was also noted. Most SC were diagnosed before or at the time of the diagnosis of IPMN. Alchool, Smoking and 1st degree FH of cancer may be associated with an increased risk of SC.
P.1.31 VARIANTS OF THE OBESITY-ASSOCIATED FTO GENE AND COLORECTAL CANCER RISK IN ITALY E. Tarabra 1 , G. Actis ∗ ,2 , E. Borghesio 2 , G. Tappero 2 , L. Framarin 2 , M. Fadda 3 , P. De Paolis 4 , A. Comandone 5 , R. Coda 6 , F. Rosina 2 1 Center
for Predictive Medicine, Presidio Sanitario Gradenigo, Torino, Italy; & Epatologia - Presidio Sanitario Gradenigo, Torino, Italy; 3 Dipartimento di Nutrizione Clinica - Ospedale Molinette, Torino, Italy; 4 Divisione di Chirurgia- Presidio Sanitario Gradenigo, Torino, Italy; 5 Divisione di Oncologia - Presidio Sanitario Gradenigo, Torino, Italy; 6 Istopatologia - Presidio Sanitario Gradenigo, Torino, Italy 2 Gastroenterologia
Background and aim: Second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be associated with obesity. Aim of the study was to establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma. Material and methods: 622 subjects who underwent colonoscopy from July 2001 to July 2008 were enrolled in the study and divided in 3 groups according to endoscopic, histologic and clinical findings: CRC (203 pts, M/F 116/87, mean age 65±11 yrs), colorectal adenoma (112 pts, M/F 61/51, mean age 62±13 yrs), healthy controls (307 pts, M/F 151/156, mean age 58±13 yrs). Rs9939609 was genotyped by real-time PCR. Results: Genotype frequencies did not deviate from the Hardy-Weinberg predictions. The FTO rs9939609 A allele frequency was 0.448, 0.449, and 0.411 for the controls, CRC and polyps patients respectively. In the healthy subjects, the FTO variant associated to the risk of obesity defined by the presence of the A allele (AA + AT genotypes) - was 69.38% (213/307); the FTO variant associated to low-risk of obesity - defined by TT genotype - was 30.62% (94/307). The proportion of individuals bearing the risk allele (AA or AT genotypes) was 72% (146/203) and 62% (69/112) in CRC and polyp patients. Compared to controls the obesity-associated FTO variant (AA genotype) had no significant effect on the risk for either CRC (OR=1.498; CI 95%=0.9872.276; p= 0.063) or colorectal adenomas (OR=0.708; CI 95%=0.451-1.112; p=0.158). In both CRC and colorectal polyps there were no differences on genotype frequency between age at diagnosis, genders and disease site. Conclusions: The obesity-linked FTO variants do not seem to play a significant role in modulating the colorectal cancer risk in the Italian population. However, highlighting a borderline significance, statistical elaboration of the data leaves a door open to interpretation. The study was supported by Regione Piemonte Italy – Direzione Sanità – Ricerca Sanitaria Finalizzata – Protocollo n. 2472/DA2001.
P.1.32 APPROPRIATENESS OF SURVEILLANCE COLONOSCOPY AFTER ADENOMA REMOVAL IN COLORECTAL CANCER (CRC) SCREENING PROGRAMME F. Monica ∗ ,1 , C. Fedato 2 , M. Zorzi 2 , C.S.G. Veneto Endoscopic 2 1 Ospedale
S. Bassiano, Bassano Del Grappa (VI), Italy; 2 Registro Tumori Del Veneto, Padova, Italy Background and aim: CRC screening programmes based on fecal occult blood test (FOBT) and colonoscopy (CS) detect an high number of individuals with adenomas, but little is known about appropriateness in these patients (pts). Aim of this study is to evaluate the appropriateness of timing of surveillance CS in CRC screening programmes in Veneto Region. Material and methods: Data collected in 2009 from 12 screening programmes in Veneto were retrospectively analyzed using the regional database. In FOBT+ve subjects undergoing CS, endoscopic and istopathological data were recorded and indication for surveillance interval, advised by endo-