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Abstracts Text


F.A. Allaert
Chaire d'evaluation medicale esc cen nutriment Dijon, Dijon, France
Objectives: In association with alcohol intake reduction, to evaluate versus placebo the improvement of the hepatic function (main objective) induced by Han Hepa® ((plants extracts and nutriments among which Lycium Chinense) Methods: controlled, double blind, randomised versus placebo study. Inclusion criteria: patients presenting an increase of the transaminases>2 times the value of reference. The main criteria was the ASAT and ALAT plasmatic values. Results: 46 patients (24 in the Han Hepa® group (HHG) and 22 in the placebo group (PlG) were included. After 12 weeks, results show a statistically higher decrease of the ALAT in the HHG than in the PlG: -44.3 ± 47.8 vs -8.5 ± 65.4 (p:0.0389) corresponding respectively to reductions of 39.4% and 9.5% of the inclusion values which is significant (p<0.0001) in the HHG and not in the PlG (p:0.5465). A decrease of at least 50% of the ALAT is present in 41.7% of the HHG versus in 18.2% of the PlG (p:0.08). A statistically higher decrease of the ASAT in the HHG than in the PlG is also observed: -50.7 ± 65.0 vs -9.6 ± 37.6 (p:0.0129) corresponding respectively to reductions of 50.2% and 13,7% of the inclusion values which are significant (p : 0,0009) in the HHG and not in the PlG (p:0.2430). A decrease of at least 50% of the ASAT is present in 41.7% of the HHG versus in 13.6% of the PlG (p=0,03). Conclusion. In association with alcoholic consumption reduction, Han Hepa® contributes to significantly restore the hepatic function.

M. Benes, T. Hucl, P. Wohl, P. Stirand, P. Drastich, J. Spicak
Department of Gastroenterology and Hepatology IKEM, Prague, Czech Republic

The most commonly used indicators of quality of colonoscopy. More complex and precise criteria such as histologtically complete endoscopic mucosal resection rate (HCEMR) have been used nowadays. However, HCEMR is no applicable to most colonoscopies where polyps are removed by polypectomy. Aim and Method: The aim of our study was to evaluate and compare various indicators of quality of colonoscopy in a retrospective analysis of all colonoscopies performed in one center between 2009 and 2012. All colonoscopies were performed by 6 experts, each of them performing at least 250 colonoscopies/year and more than 1000 colonoscopies in their carrier. The data were statistically evaluated using correlation tests (Spearman's coefficient). Results: Altogether, we evaluated 3852 consecutive colonoscopies The mean caecum intubation rate (CR) was 97% (range 93% - 98%), the mean terminal ileum intubation rate was 90% (range 87% - 93%), the mean adenoma detection rate (ADR) was 33% (range 21% - 42%), the mean colorectal cancer detection rate was 4% (range 3% - 5%), the rate of flat lesion detection was 8% (range 5% - 11%). In total 342 EMR were carried out in 325 patients. The percentage of histologically complete EMR (complete removal of lesion with histologically proven margin free of neoplasia, HCEMR) of significant polyps and flat lesions was 42% (21%-63%). The mean percentage of complications after EMR was 2% (range 1% - 3%). In total 1351 polypecomies of significant polyps (greater than 1cm) were carried out. The mean histologically complete polypectomy rate (HCPR) of significant polyps was 51% (range 32% - 69%). The HCPR significantly correlated with ADR, CR and HCEMR. Conclusion: Histologically complete polypectomy rate (HCPR) appears to be completely comparable with histologically complete EMR rate (HCEMR) and could an ideal indicator of quality of colonoscopy.

M. Benes, T. Hucl, P. Drastich, P. Stirand, P. Wohl, J. Spicak
Department of Gastroenterology and Hepatology IKEM, Prague, Czech Republic

Introduction: Colonoscopy is considered to be the gold standard for colon evaluation and screening for colorectal cancer (CRCA). Classical colonoscopy (CC) is an invasive method with an unfavourable reputation amongst patients which may be a reason for noncompliance with CRCA screening programs. Colon capsule endoscopy (CCE) is an innovative non-invasive technique which has gained patients interest in CRCA screening despite the fact of being very costly. Aim and methods: The aim of this prospective, multicentric study was to assess reasons for preference for CCE over CC. The data from all consecutive patients scheduled to undergo CCE were obtained using a questionnaire. Results: From December 2010 to October 2012 one hundred patients (68 men, 32 women, average age 52 years) were included in the study. Seventy eight (78%) patients had university education and 20 patients (20%) were high school graduates. Seventy nine (79%) were senior managers with at least 10 or more employees. Sixty five (65%) had their salary at least four times the nation's average income. The main reasons of CCE preference were concerns about a patient`s privacy and embarrassment (38 patients, 30 males, 8 females), concerns of pain (35 patients, 18 males, 17 females), fear of a loss of discernment (20 patients, 15 males, 5 females). Forty six (46%) patients had undergone CC in the past. In this subgroup, privacy issue was main reason for 33 (71%) patients and pain for 13 (28%) patients. Forty two patients (42%) would never undergo a screening CC even though 19 (45%) of them had a positive family history. Conclusions: The main reason for CCE preference over CC was mental discomfort and fear of embarrassment during CC, rather than concerns of pain.

A. Botma1,9, B. Diergaarde2, F.M. Nagengast3, F.J. van Duijnhoven1, R.M. Winkels1, B.J.M. Witteman4, H.F.A. Vasen5,6, E. Kampman1,7,8
1Division of Human Nutrition, Wageningen University, Utrecht, The Netherlands
2University of Pittsburgh Cancer Institute, and Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America
3Department of Gastroenterology & Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
4Department of Gastroenterology, Hospital Gelderse Vallei Ede, Ede, The Netherlands
5Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands
6Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, Leiden, The Netherlands
7Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
8Department of Health Sciences, VU University Amsterdam, Amsterdam, The Netherlands
9Currently at the Department of Preventive Oncology, National Center for Tumor diseases & German Cancer Research Center, Heidelberg, Germany

Purpose: Higher body mass index (BMI) is an established risk factor for colorectal adenomas and cancer. High BMI may alter exposure to insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and so affect colorectal tumor risk. Functional polymorphisms in IGF-axis genes may modify the relationship between BMI and colorectal tumors. We evaluated associations of BMI, common single nucleotide polymorphisms (SNPs) in IGF-axis genes, and their interactions with recurrence of colorectal adenomas in a prospective study. Patients and Methods: Adenoma cases (N=515) from a Dutch case-control study (the POLIEP-study), were prospectively followed for adenoma recurrence. Median person-time was 4.5 years. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated to evaluate associations between BMI, 37 common SNPs in 8 IGF-axis genes and adenoma recurrence. Results: BMI was not associated with colorectal adenoma recurrence. Two evaluated SNPs, rs3213221 in IGF2 and rs3763497 in IGFBP1, were statistically significantly associated with developing recurrent advanced adenomas (heterozygotes + rare allele homozygotes versus common allele homozygotes; rs3213221, HR: 4.18 95%CI:1.46-11.95; rs3763497, HR: 2.20 95%CI:1.01-4.79). For rs1003483 and rs1004446 in IGF2, risk of any adenoma recurrence among normal weight individuals was higher for those with at least one rare allele, while among overweight or obese individuals the risk of recurrence was higher for common allele homozygotes. Conclusion: Our results suggest that common variation in IGF-axis genes influence the likelihood of colorectal adenoma recurrence and may modify the association between BMI and colorectal adenoma recurrence. This work was supported by the Dutch Cancer Society (grant UW-2005-3275)

R.N.A. Bruck1, 2 P. Halfon3, I. Goldiner1, S. Zelber-Sagi4,
Z. Halpern1,2, R. Oren1,2, A. Shlomai1,2
1Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
3Alphabio Laboratories, Marseille, France
4School of Public Health, University of Haifa, Haifa, Israel

Background: Serum bile acids (SBAs) are commonly elevated in cholestatic liver diseases, but it is unclear if SBA levels are also elevated in non-cholestatic chronic liver diseases and whether levels correlate with disease severity. Methods: We analyzed SBA levels of 135 consecutive patients with chronic hepatitis C infection and correlated these levels with the degree of liver fibrosis determined by liver biopsy. In addition, we assessed the accuracy of SBA levels as predictor of liver fibrosis by comparison to patients' FibroTest scores. Results: Two-thirds (90/135 patients, 67%) of patients had non-severe liver fibrosis (Metavir F0-F2) and the others (45/135, 33%) had severe fibrosis or cirrhosis (Metavir F3-F4). Over 80% of patients had genotype 1 HCV. The SBA levels were significantly higher in patients with severe fibrosis compared to non-severe fibrosis (11.46 10.01 versus 6.37 4.69, P < 0.0001). Furthermore, a ROC curve based on a model that included serum bile acids, age, BMI, serum AST, glucose and cholesterol levels suggested that this combination reliably predicts the degree of liver fibrosis, and is not inferior to the FibroTest score (P = 0.87). We found no significant correlation (p=0.57) between HCV viral load and the SBA levels among the 30 patients in which SBA levels were obtained at the same time with the viral load. Conclusions: Measurement of SBA levels may have a clinical role as a non-invasive tool to assess the severity of HCV-induced liver disease. Combined with other laboratory parameters, SBA levels predicts fibrosis severity with high degree of accuracy.

M. Crha1, J. Hlavsa2, T. Grolich2, A. Hep3, A. Necas1
1CEITEC VFU, Brno, Czech Republic
2Surgical Clinic of the University Hospital Brno Bohunice, Brno, Czech Republic
3Endoscopic Clinic of the University Hospital Brno Bohunice, Brno, Czech Republic

The study was undertaken to verify the technique of delivery and deployment of a new covered biodegradable (BD) stent into the esophagus of miniature pigs as well as to evaluate tissue reaction after stent implantation. Covered polydioxanon stents (flare/body/flare x length: 31/25/31 x 80 mm) were endoscopically implanted in 8 miniature pigs. The stents were packed separately and loaded into the delivery device (28F diameter, 75 cm length) prior to implantation. Endoscopic check-ups were performed at 2, 4, 6, 8, 10 or 14 weeks after implantation. The animals were euthanized during the final week of monitoring and the esophagus was histopathologically examined. The esophageal stent implantation was a technically straightforward and simple procedure. The implanted stents were often displaced (n=6; 75%) by week 2 following surgery; mucosal hyperplasia was minimal, however. Stent discolouring was observed from week 2; stent resorption occurred from weeks 10 to 12. Stent implantation resulted in macroscopic and histopathological diagnosis of local esophagitis. Esophageal mucosa healed completely upon stent resorption (observed in week 14). Implantation of the covered BD stent never led to esophageal rupturing in test subjects, despite one experiencing an unexpected stent fragmentation leading to esophageal obstruction. The covered biodegradable stent can be regarded as a potentially safe implant to be endoscopically applied into the esophagus. More comprehensive research should include preclinical stent testing in esophageal stricture treatment in a larger population of experimental animals.

M. Dovizio1, S. Alberti1, A. Sacco1, S. Schiavone1, A. Sgambato2,
T.J. Maier3, D. Steinhilber3, P. Patrignani1
1Department of Neuroscience and Imaging, "G. d'Annunzio” University, Chieti, Italy
2Institute of General Pathology, Catholic University, Rome, Italy
3 Institutes of Pharmaceutical Chemistry, Frankfurt University, Frankfurt, Germany

Twist-1 plays a key role in epithelial-mesenchymal transition(EMT) and metastasis by repressing E-cadherin-mediated cell-cell adhesion and inducing mesenchymal markers and cell motility. Prostaglandin(PG)E2 signaling mediates EMT and cell migration/invasion. We aimed to address the hypothesis that:(i)tumor cell/platelet cross-talk induces PGE2 release which may play a role in Twist-1 mRNA up-regulation and E-cadherin mRNA down-regulation, and (ii) selective inhibition of platelet-dependent PGE2 by aspirin may affect these changes in gene expression. Co-cultures with human colon carcinoma cells (HT29) and platelets were performed for 20 h. In some experiments, platelets were pretreated with aspirin(300 microM), to completely suppress cyclooxygenase(COX)-1 activity. HT29 expressed PGE2 receptors(i.e.,EP1, EP2 and EP4, but not EP3 and thromboxaneA2 receptor). Exogenous PGE2(1.5 ng/ml) added to HT29 cells induced a significant increase of Twist-1 mRNA and down-regulation of E-cadherin mRNA. In platelet-HT29 co-cultures, PGE2 release(1.3+0.1 ng/ml) was higher than in platelets and HT-29 cultured alone. In co-cultures, HT-29 mRNA levels of Twist-1 were significantly increased by 4-fold while E-cadherin mRNA levels were significantly reduced by 42% versus HT-29 cultured alone. Aspirin pre-treatment of platelets prevented the changes of Twist-1 and E-cadherin mRNA levels in HT29 and they were rescued by the addition of PGE2. In conclusion, selective inhibition of platelet COX-1-dependent PGE2 by aspirin prevented enhanced expression of Twist-1 and down-regulation of E-cadherin caused in HT29 cells by platelet interaction. These results open the way to study in animal models and patients the role of this mechanism in the anti-metastatic effect of low-dose aspirin detected in clinical trials.

M. Dovizio1, T.J. Maier2, S. Alberti1, L. Di Francesco1,
E. Marcantoni1, G. Münch3, C.M. John4, B. Suess5, A. Sgambato6,
D. Steinhilber2, P. Patrignani1
1Department of Neuroscience and Imaging and Center of Excellence on Aging (CeSI), "G. d'Annunzio” University, Chieti, Italy
2Institutes of Pharmaceutical Chemistry, Frankfurt University, Frankfurt, Germany
3CorImmun GmbH, Martinsried, Germany
4MandalMed, Inc., San Francisco, California, United States of America
5Fachbereich Biologie, Technische Universität Darmstadt, Darmstadt, Germany
6Institute of General Pathology, Catholic University, Rome, Italy

Cyclooxygenase(COX)–2–derived prostanoids can influence several processes that are linked to carcinogenesis. We aimed to address the hypothesis that platelets contribute to aberrant COX-2 expression in HT29 colon carcinoma cells and to reveal the role of platelet-induced COX-2 on the expression of proteins involved in malignancy and marker genes of epithelial-mesenchymal transition(EMT). Human platelets co-cultured with HT29 cells rapidly adhered to cancer cells and induced COX-2 mRNA expression, but not protein synthesis which required the late release of platelet PDGF and COX-2 mRNA stabilization. Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in down-regulation of p21WAF1/CIP1 and up-regulation of cyclin B1, since these effects were prevented by rofecoxib(a selective COX-2 inhibitor) and rescued by exogenous PGE2. Galectin-3, highly expressed in HT29 cells, is unique among galectins because it contains a collagen-like domain. Thus, we studied the role of galectin-3 and platelet collagen receptors in platelet-induced COX-2 overexpression. Inhibitors of galectin-3 function(beta-lactose, a dominant-negative form of galectin-3,Gal-3C, and anti-galectin-3 antibody M3/38) or collagen receptor-mediated platelet adhesion(revacept, a dimeric collagen receptor GPVI-Fc) prevented aberrant COX-2 expression. Inhibition of platelet-cancer cell interaction by revacept was more effective than rofecoxib in preventing platelet-induced mRNA changes of EMT markers suggesting that direct cell-cell contact and aberrant COX-2 expression synergistically induced gene expression modifications associated with EMT. In conclusion, our findings provide the rationale for testing blockers of collagen binding sites, such as revacept, and galectin-3 inhibitors in the prevention of colon cancer metastasis in animal models followed by studies in patients.

Petrozavodsk State University, Petrozavodsk, Russia

Introduction: It is not always possible due to different reasons to perform liver biopsy in order to diagnose nonalcoholic steatohepatitis (NASH). Physicians often estimate the hepatocellular inflammation using conventional laboratory tests. The aim of this study was to estimate the frequency of detection of hepatocellular inflammation using laboratory indicators in histologically confirmed NASH. Materials and methods. 32 patients were examined with histologically confirmed NASH: 19 (59,4%) females and 13 (40,6%) males. Steatosis grading was estimated using the Brunt method, histological activity index (HAI) was defined by the Knodell method, and fibrosis (F) by the Metavir method. Laboratory tests of hepatocellular inflammation included alanine aminotransferase (АLТ), aspartate aminotransferase (АSТ), bilirubin, ɤ-globulins, and ESR. Results. Body mass index was 32,6±3,5 kg/m2. 16 (50,0%) patients had diabetes mellitus. Steatosis grading by Brunt was 1,8±0,77, HAI 5,9±0,4 and F 0,86±0,53. Level of ALAT amounted to 70,6±8,7 U/l, ASAT 41,2±9,1 U/l, bilirubin 16,2±5,8 mkmol/l, ɤ-globulins 14,2±0,6%, and ESR 15,6±3,2 mm/h. ALAT exceeded normal level in 18 (56,3%) patients, АSAT in 7 (21,9%), bilirubin in 6 (18,8%), ɤ-globulins in 5 (15,6%) and ERS in 5 (15,6%) patients. Hepatocellular ballooning, macrovesicular steatosis, necrosis, intralobular and portal inflammation were detected by histological analyses in all 32 (100%) patients. Conclusion. The main laboratory indicator of hepatocellular inflammation, ALT, was increased only in 56,3% of patients with histologically confirmed NASH, arguing for the great significance of histological analysis in NASH.

A. Farrukh, J.F. Mayberry
Department of Digestive Diseases, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

Methods: Data were collected from a central register of patients who received biologic therapy for Crohn's disease between 2008 and 2012. The register does not record details of patients for whom biologic therapy was considered inappropriate. The patients' gender and ethnicity were noted from the register. One hundred and thirty nine patients received treatment during this period, of whom, 126 were of English origin and 13 South Asian. The expected numbers of patients from either a South Asian or English background were calculated from work done on the prevalence of Crohn's disease in these communities in Leicester in the 1990s. The expected prevalence in the South Asian community at that time was 33/105 population and that in the English community was 76/105. Recent work from elsewhere would suggest a higher prevalence in both communities and also that the disease may be reaching comparable levels of frequency. Results: Based on this conservative epidemiological data 42 patients from a South Asian background could have been expected to receive biological therapy, whereas in practice only 13 did (z = -4.4 p < 0.0001). However, within the groups the choice of infliximab versus adalumimab as the drug of choice was comparable (z = -0.6 n.s.). In addition there was no difference in the gender distribution of those who received treatment between the two communities. (z = -0.5 n.s.) It appears patients with Crohn's disease of South Asian origin are less likely to receive appropriate biologic therapy than their English counterparts. There is support for this view from the internal consistency in that there are no differences in the type of treatment given or in the gender distribution. This finding mirrors the experience of patients with ulcerative colitis.

A. Farrukh, J.F. Mayberry
Department of Digestive Diseases, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

The experience of patients from diverse ethnic groups who were diagnosed with ulcerative colitis between 1996 and 1998 in Leicester, UK and their subsequent care over a decade were reviewed. By the year 2012 ethnic groups in Leicester, UK will make up the majority of the population. 263 potential cases were identified, of whom 70 met the inclusion criteria. Data were collected on age, gender, ethnicity, religion, frequency of consultation with a senior doctor, number of hospital admissions, number of substantial procedures, such as surgery, screening colonoscopy, discharge rates and deaths. 28 patients were of Asian origin and 42 were non-Asians. Asian patients were seen less frequently by senior doctors and were discharged significantly more often than non-Asian patients (63% v 32% p < 0.02). They also underwent less substantial procedures (2.03 v 2.92, p < 0.04). Screening colonoscopy also occurred less often (35% v 46%), but this did not reach statistical significance. Despite evidence of poorer overall care the rates of surgery and mortality were similar in both groups. However, this study emphasises the fact that over significant periods people from minority groups do not experience equal access to health care and this is in line with studies in other disease groups. Clearly there is a need to ensure that patients from diverse groups are able to influence the way in which they receive care and that their access to healthcare is comparable to other members of our communities.

J.W. Frost, J.F. Mayberry
Leicester General Hospital, University Hospitals of Leicester, Leicester, United Kingdom

Aims: There is limited information surrounding patient understanding of inflammatory bowel disease (IBD). It is uncertain whether patient concerns are adequately addressed during consultations. The aim of this study was to ask patients to consider what their specific concerns were and to document them so that they could be specifically addressed. This would also allow clinicians to reflect on potential shortfalls in patient education, and influence future practice towards highlighted needs. Methods: Using a simple pro-forma prior to clinic, 70 patients were asked to list those questions most important to them during that consultation. The suggested number of questions was 3 but responses varied from 0 to 6. These were then answered, either through direct response during clinic time, or via subsequent patient correspondence. Results: A total of 188 questions were asked with only 1 out of the 70 patients not making a list. Twenty nine per cent of questions pertained to medications and potential side effects, whereas only 7% concerned disease progression and future treatment. In addition to medication queries, a wish to review investigation results, information on current symptoms (intestinal and extra-intestinal) and dietary information outweighed other concerns, scoring 13%, 25% (14+11), and 8% respectively. Conclusions: A large proportion of patients' information needs relate to medications and investigations they are undergoing. We therefore need to provide more time in explaining aims and potential risks involved with various treatments, and providing them with results early in order to alleviate anxiety and uncertainty.

M. Gimenez, G.O. Patron, P. Nieto, A. Hernandez, F. Damaso,
R.A. Bendezu, J.M. Ruiz, J.L. Vega, M.A. Rodriguez, D. Tello
Torrecardenas Hospital Almeria, Almeria, Spain

Objective Evaluating the occurrence of immediate adverse effects in biological therapy for IBD. Methodology A retrospective evaluation was done of immediate adverse effects with biological therapy in CD and UC. A total of 92 patients were enrolled (61 treated with IFX and 31 with ADA) who were being followed on a regular basis by the Inflammatory Bowel Disease Unit at Torrecárdenas Hospital in Almeria, Spain. Results In the IFX cohort, adverse effects were observed in 16.4% of patients with CD and in 13.1% of those with UC, the most common being abdominal pain and immediate post-injection reactions. With ADA, adverse effects were observed in 12.9% of CD and 22.6% of UC patients, the most common being tachycardia, abdominal pain, and a feeling of weakness. Age, sex, and duration of the disease were not factors predisposing to the appearance of adverse effects, these results being statistically significant. However, bio-naïve patients in the IFX cohort were more susceptible to immediate effects than those in the ADA cohort. No severe adverse effects (i.e. anaphylactic shock, respiratory insufficiency, etc.) were observed. In both cohorts, there were only 2 cases where treatment was discontinued due to reactions at the injection site. Conclusions: Only mild adverse effects were observed in the great majority of patients, the highest incidence being seen in UC patients in the ADA cohort. The adverse effects did not result in any significant suspension of treatment. Bio-naïve IFX patients could be more susceptible to immediate adverse effects and, therefore, would benefit from pre-medication.

T. Hucl1, M. Benes1, M. Kocik2, J. Maluskova3, E. Kieslichova4,
M. Oliverius2, J. Spicak1
1Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
2Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
3Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
4Department of Anesthesiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Background: Over the scope clip (OTSC) has become a widely accepted technique of transluminal closure in NOTES. However, the usual clip application is based on mucosa approximation and does not fulfill the surgical principle of serosa-to-serosa approximation in hollow organ closures. The aim of the study was to evaluate the feasibility, safety and efficiency of serosal OTSC closure in comparison to the standard mucosal OTSC closure. Methods: Animals were randomized to receive either mucosal (10 animals) or serosal (10 animals) OTSC closure. In mucosal closure, the mucosal portions of the incision edges were approximated by a double grasper and pulled into the clip's cap, whereas in serosal closure, the serosal portions of the incision edge were grasped, approximated and pulled into the cap. Results: All OTSCs were applied successfully in a mean time of 5.3 min (range 2-7 min) in the mucosal group and in a mean time of 8.8 min (range 4-12 min) in the serosal group (p=0.001). Necropsy demonstrated patent full-thickness gastric closure with no macroscopic signs of infection in all animals. Histologically, the mucosal closure was characterized by an end to end apposition of the gastric wall layers, whereas the serosal closure was characterized by a side to side apposition of the layers.

Conclusions: Serosal OTSC closure was feasible, safe and efficient. It required a longer time to perform due to increased technical difficulty. Serosal OTSC closure does not seem to add any benefit to the standard mucosal OTSC closure.

S. Jamil, K. Usmanghani, A. Saeed
Faculty of Eastern Medicine Hamdard University Karachi Pakistan, Okara, Pakistan

Drug-induced Hepatitis is one of the most common causes of liver damage or fulminant liver failure. In this study the benefits and curing effect of herbomineral drug which contains hartal warqi (the crude arsenic trioxide mineral) along with Zingiber officinale, Piper nigrum and ammonium chloride is studied in order to cure advance stage liver diseases. 36 White albino New zeland rabbits of both genders weighing about 2.0-2.5 kg. Rabbits were divided into two groups of 18 animals and then further into four groups of 9,9 animals. No side effects were at all recorded in the test group. Overall success was observed in test group. On the basis of serologic tests, immune tests and tissue studies it can be observed that all the animals of both test groups gained their normal health in about 60 days as compared to the animals of control group who were still suffering and most of them died, as their immunity failed to recover them from the injury developed by different. The data so acquired clearly exhibit that Hepcon is an effective medicine of liver. There was no any side effect associated with Hepcon. Hepcon is very well tolerated by all the animals so it is very safe drug to use in liver diseases. Although it is a general assertion that Hartal warqi either as single ingredient or in combination with herbal drugs is devoid of any toxicity but on the other hand beneficial effects to ward of liver malaise has been adequately proved.

H. Korkmaz1, L. Kebapcilar2
1Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Gastroenterology, Selcuklu, Konya, Turkey
2Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Selcuklu, Konya, Turkey

Introduction: Acute hepatic failure is usually defined as the severe impairment of hepatic function in the absence of preexisting liver disease. Various unusual presentations in patients with thyroid storm have been described but acute liver failure is extremely rare. We present a case in which multiorgan dysfunction was associated with methimazole and thyroid storm. Case: A 41-year-old man with a history of hyperthyroidism had been treated with methimazole and propranolol for the past 2 months. He developed multiorgan dysfunction with acute liver failure, severe lactic acidosis, disseminated intravascular coagulation, heart failure and acute pulmonary edema with rapid deterioration of renal function. The patient had no history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. This case illustrates the sudden and abrupt deterioration of multiorgan dysfunction due to antithyroid drug administration and thyroid storm. The thyroid storm score of Burch and Wartofsky was 90/140. The multiorgan dysfunction was reversed by discontinuation of the methimazole and treat with hemodialysis, steroids, cholestyramine, nonselective beta-blocker, fresh frozen plasma infusion and supportive management in the intensive care unit. The patient was discharged from the hospital with normal coagulation parameters, renal and liver function tests. Conclusion: This case highlights the importance of regular monitoring of liver function for patients who receive methimazole therapy for hyperthyroidism; Methimazole and thyroid storm might be complicated by multiorgan failure, especially during the first 2 months after initiating therapy.

H. Korkmaz1, L. Kebapcilar2
1Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Gastroenterology, Selcuklu, Konya, Turkey
2Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Selcuklu, Konya, Turkey

Introduction: Advances in reconstructive head and neck surgery have prompted radical approaches to the treatment of pharyngeal and laryngeal carcinoma. Pharyngo-esophageal reconstructive surgery often needs the use of skin-muscle grafts to restore both the anatomy and function of the intervened area. We herein report a rare case who experienced dysphagia secondary to hair growth in the esophagus after receiving this type of surgery. Case: A 61-year-old man presented to our clinic with progressive dysphagia of 4 weeks duration. He had history of laryngeal cancer with total laryngectomy with bilaterally selective neck dissection nine months ago after a failed radiotherapy. Also his history revealed a pharyngocutaneous fistula postoperatively and a pectoralis major myocutaneous flap reconstruction for the fistula, three months later the first operation. Esophageal endoscopic examination revealed an intact skin graft in the hypopharynx and proximal esophagus with the epithelial surface bearing hair as well as a proximal esophageal stricture. Cervical computed tomography showed no pathological findings except flap. Endoscopic dilatation of the stricture resulted in improvement of symptoms. Conclusion: Curative treatments of pharyngeal and laryngeal carcinoma often require removal of large portions of the hypopharynx and esophagus. With extensive surgical resection, full-thickness skin grafts are often used to reconstruct the removed portions. As these epithelial structures become the inner surface of the reconstructed tube, these flaps may continue to bear hair. This may give rise to a sensation of dysphagia and a characteristic endoscopic appearance seen in postsurgical endoscopies.

H. Korkmaz1, L. Kebapcilar2
1Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Gastroenterology, Selcuklu, Konya, Turkey
2Selcuk University, Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Selcuklu, Konya, Turkey

Background/Aim: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of soluble CD40 ligand, leptin, oxidative stress and body composition in patients with dyspepsia infected with H. pylori. Methods: The infection of H. pylori was based on the presence of both 14C urea breath test (UBT) and histology. Patients were given triple eradication therapy for 14 days and at 3 months after the treatment, 14C UBT was reinstituted. Fasting glucose, leptin, body composition, soluble CD40 ligand, total oxidant status (TOS) were studied before and at 3 months after the treatment. Results: In 33 subjects, H. pylori infection was successfully eradicated. sCD40L and TOS levels were significantly decreased after H. pylori eradication. The percentage of body fat and body fat mass significantly decreased whereas the fat free mass (FFM) increased after eradication. However, eradication of the organism yielded no differences in leptin levels. Conclusion: These findings suggest that H. pylori eradication reduces the sCD40L and oxidative stress, fat mass with a significant increase in fat free mass. Thus, eradication of H. pylori infection not only improves ulcer healing, but may also reduce the presumed atherosclerosis risk.

A.G. Korotkevich1, A.S. Leontiev2, O.R. Efremova2, M.A. Shadrin3
1Novokuznetsk State Institute of Advanced Medical Education, Novokuznetsk, Russia
2Clinical Hospital Nr. 29, Novokuznetsk, Russia
3Clinical Hospital Nr. 22, Novokuznetsk, Russia

Aim: Evaluate the effectiveness of endoscopic hemostasis in variceal bleeding prior to the Blackmore probe. Materials and methods. A multicenter randomized trial. From June 2011 to June 2012. With active bleeding from esophageal varices at 46 people a choice of primary hemostasis method defined odd / even day hospitalization. Hemostasis was performed by submucosal infiltration of solution through the injector. Primary hemostasis carried out by infiltration hemostasis + Blackmore probe in 19 patients (group 1), by Blackmore probe in 10 patients (group 2); infiltration hemostasis by 1% solution of H2O2 in 7 patients (group 3) or by 0.9% NaCl solution at 10 patients (group 4). Results. Primary hemostasis was effective in first group in 19 patients (100%) in group 2 in 9 (90%); in group 3 in 1 (14%); in group 4 in 3 cases (30%) (1vs2-χ2 = 0 , 04, p = 0,8514; 2vs3 - χ2 = 0,00, p = 0,9461; 3vs4 - χ2 = 1,53; p = 0,2162). Rebleeding before sclerotherapy occurred in 1st group in 2 patients (11%); in group 2 in 7 (70%); in group 3 in 6 (86%); in group 4 in 7 cases (70%) (1vs2-χ2 = 10,87, p = 0,001; 2vs3 and 3vs4 no difference). Secondary prevention session of sclerotherapy performed in first group in 9 patients (47%); in group 2 in 6 (60%); in group 3 in 4 cases (57%); in group 4 in 7 (70%) (1vs2; 2vs3; 3vs4 no difference). Overall mortality 1vs2 χ2 = 3,80 p = 0,0511 2vs3 χ2 = 4,50 p = 0,0340; 3vs4 χ2 = 0,78 p = 0,3770. Conclusions. The effectiveness of primary hemostasis by infiltration exceeds Blackmore probe on the number of rebleeding and overall mortality. Using the probe Blackmore after primary hemostasis infiltration also improves patient outcomes.

T.I. Kovac
Hospital Kasindo, Eastern Sarajevo, Bosnia and Herzegovina

Introduction: Hypomagnesemia as adverse effect of PPI is often underrecognised in clinical practice. It can be expected more often with long term application in patients with significant comorbidity and comedication with digitalis and diuretics. Here is the presentation of a diabetic patient on haemodialysis, taking digitalis, who received high doses of PPI during ten months and during that period had twice serious cardiac arrhythmia. Method: Patient is a woman, 50 years old on chronic dialysis because of complications of diabetes and polycyctic kidney disease. She complained on intermitent nausea and epigastric pain and underwent upper endoscopy. She was adviced to take PPI because of GERB for 4 weeks, but she continues taking medicament for a few months. Results: During next 10 months patient had two episodes of cardiac arrhythmia, with nausea and vomiting. First time the level of serum Mg was normal and etiology of arrhythmia was not cleared. She recovered with symptomatic therapy, supplementation of Mg and withdrawel of PPI. 8 weeks after repeated introduction of PPI she had again episode od arrhythmia, this time with low level of serum Mg. After correction of Mg, the arrhythmia resolved. Conslusion: Hypomagnesemia is not so rare adverse effect of long term application of PPI. The level of magnesium shoud be regularly monitored at least in at-risk patient i.e. dialysis, diabetics, hyperthroidismus, comedication with digitalis and diuretics. The tests for determining level of Mg are not available in many smaller hospitals, and there are no precise recommendations for monitoring.

R.E. Langley1, R.H. Wilson2, A. Ring3, H.G. Kynaston4,
C.M. Murphy1, D.A. Cameron5, F.H. Cafferty1, M.K. Parmar1
1Medical Research Council Clinical Trials Unit, London, United Kingdom
2Queen's University, Belfast, United Kingdom
3Sussex Cancer Centre, Brighton, United Kingdom
4Cardiff School of Medicine, Cardiff, United Kingdom
5University of Edinburgh, Edinburgh, United Kingdom

Recent evidence has led to the re-evaluation of aspirin as a potential anti-cancer therapy: meta-analyses of randomised cardiovascular trials of aspirin show beneficial cancer effects including a reduction in metastases (1); the randomised CAPP2 trial demonstrated that aspirin prevents cancer in those with a hereditary predisposition (2); and data from large observational studies indicates that aspirin use after a cancer diagnosis improves both cancer outcomes and survival (3, 4). Concerns about serious haemorrhage, have limited aspirin use as a primary cancer prevention strategy, however, after cancer diagnosis and treatment (e.g. in the adjuvant setting), potential benefits - reduction in recurrent cancer and associated mortality (and cardiovascular effects), are likely to outweigh side effects. A large, international, multi-centre, randomised trial is planned. The effect of aspirin (100mg or 300 mg daily for at least 5 years) after standard primary therapy on cancer recurrence and mortality will be investigated in four common cancers (colorectal, breast, gastro-oesophageal and prostate) by means of parallel, double-blind, placebo-controlled trials. Secondary outcomes include overall healthcare benefits and toxicity. The trials are planned to recruit in the UK and India initially, opening late 2013 once full funding is secured, with the potential to expand to other countries. Trial design, rationale and translational work will be described. As an inexpensive drug with a potential therapeutic role in several common cancers, aspirin could have a huge impact on the global cancer burden.

A.S. Leontiev2, A.G. Korotkevich1, O.R. Efremova2, R.A. Plusnin 3,
E.B. Taraskina4, S.A. Yaroschuk5
1Novokuznetsk State Institute of Advanced Medical Education, Novokuznetsk, Russia
2Novokuznetsk Municipal Hospital Nr.29, Novokuznetsk, Russia
3Novokuznetsk Municipal Hospital Nr.1, Novokuznetsk, Russia
4Novokuznetsk Municipal Hospital Nr.5, Novokuznetsk, Russia
5Belovo Municipal Hospital Nr.1, Belovo, Kemerovo Oblast, Russia

Aims. We investigated results of endoscopic injections in prevention ERCP-associated pancreatitis. Materials and methods. A multicenter randomized trial. Randomization by alternating days of hospitalization. From 2004 to 2011, the standard technique of papillotomy used in ERCP at 2296 patients, at 1146 patients after ERCP we used a method for preventing pancreatitis (MPP) through the submucosal infiltration of lidocaine / novocaine solution, which was carried out by submucosal infiltration of 0.5% lidocaine or novocaine solution (10 ml) into papillotomy incision through the catheter, including those at bleeding for hemostasis. Results. In standard ERCP technique group there were 1709 patients with papilla stenosis, 294 patients with postcholecystectomy syndrome and 293 with symptomatic choledocholythiasis. In post ERCP pancreatitis prevention group 94 patients had acute bile pancreatitis, 624 papilla stenosis or sphincter Oddi dysfunction, 235 postcholecystectomy syndrome, 193 symptomatic choledocholythiasis. After ERCP and EPST we used endoscopic submucosal injection and had no cases of pancreonecrosis development. In these patients the high amilase level took place in 326 cases (28,4 %), the clinical picture of severe acute pancreatitis has arisen at 3 cases (0,26 %). Among 2296 patients without endoscopic preventive maintenance of acute pancreatitis after ERCP the high amilase level took place in 792 cases (34,5 %), the clinical picture of severe acute pancreatitis has arisen at 20 cases (0,87 %), died of pancreatitis in 5 cases (0,22%). Standard technique vs MPP=0,87% vs 0,26% (Chi-square (df =1) 4,48 p= 0,0342) The general frequency of complications Standard technique vs MPP = 3,18%vs1,3% (Chi-square (df =1) 13,20 p=0,0003). Numbers of intravenous solutions were low in 1, 6 times after endoscopic injections. Conclusions. Endoscopic injection of stimulating lymphatic vessels solutions in distal part of duodenum is very simple and effective for post ERCP pancreatitis prevention. It can decrease treatment cost in acute ERCP-associated pancreatitis.

R. Marszałek, P. Ziemiański, W. Lisik, Z. Wierzbicki, A. Chmura
Department of General Surgery and Transplantology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland

Introduction: Bariatric procedures interfere with the architecture of the gastrointestinal tract. We examined the occurrence of alterations in histological structure of the gastric mucosa, after specific type of surgery. Method: We retrospectively analyzed 65 pairs of gastric mucosa biopsy taken from morbidly obese patients between 2004 to 2011. We took 2 samples of gastric mucosa from every patient: one during the surgery and second during the routine upper gastrointestinal endoscopy 18 months after. We analyzed occurrence of histological alterations of gastric mucosa, especially presence of inflammation before and after surgery. We compared 39 patients who underwent vertical banded gastroplasty (VBG) to 26 patients after roux-en-Y gastric bypass (RYGB). Results: Gastritis in biopsy specimen taken during surgery and after 18 months has been diagnosed in 62.9% and 58.5% of patients respectively (p=0.99; NS). In VBG group gastritis was present in 69.2% at the time of surgery and in 64.1% after the operation (p=0.712; NS), while in RYGB group in 52.2% and 50.0% respectively (p=0.527; NS). We also analyzed correlation between presence of the gastritis and plasma concentration of the C-reactive protein. Conclusion: Bariatric procedures do not significantly affect the gastric mucosa. There is no significant difference between vertical banded gastroplasty and roux-en-Y gastric bypass concerning the gastric mucosa histology after The surgery. Presence of gastritis does not correlate with increased plasma C-reactive protein concentration.

G. Möslein1, C. Schneider1, R. Schneider2
1Department of General and Visceral Surgery, Bochum, Germany
2Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany

Purpose: Desmoid disease in FAP patients frequently comprises combined large mesenteric and abdominal wall tumour mass. In the light of severe morbidity and mortality caused by surgery, we investigated a less invasive approach in selected patients. Methodology: Patients with FAP and large desmoids tumours were evaluated by MRI scans. All of these patients had been on medication with high-dose tamoxifen and sulindac. Results: A total of 5 patients were included (4 males). All patients had abdominal wall mass exceeding the diameter of 15cm (15,5cm–42cm) and additionally mesenteric desmoid tumour. In the preoperative scans, the abdominal portion of the mass appeared to have a sheath separating the tumour masses in 2 cases; in 3 cases there was a narrow connection of tissue. In 3 cases the histological margin towards the mesenteric desmoid was involved, indicating a R1 or R2 situation. In the 2 R0 cases, the margin was minimal (1mm versus 3mm). All patients were kept on the medication with high-dose tamoxifen and sulindac after a perioperative pause of 2 weeks (one week prior and one week after surgery). No recurrence of the abdominal wall desmoids was observed within the follow-up of 12-23 month. Conclusion: Partial resection of large abdominal wall desmoids under protective medication with high-dose tamoxifen and sulindac does not lead to recurrence or has a negative impact on existing mesenteric desmoids. Therefore in a selected group on patients with large abdominal wall desmoids and distorting physical appearance partial desmoids removal may be a new and attractive concept.

G. Möslein1, C. Schneider1, R. Schneider2
1Department of General and Visceral Surgery, Bochum, Germany
2Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany

Purpose: In Lynch syndrome patients screening recommendations differ internationally and are subject to continuous modification. We investigated international expert opinion, insinuating diagnosis of a pathogenicMMR mutation. Methodology: A questionnaire was designed in the format of a monkey survey anddistributed on behalf of InSiGHT (International Society for Gastrointestinal Hereditary Tumours) and the Mallorca Group (EIGHT). Results: Of 147 responses, 27.7% were from gastroenterologists, 32.5% surgeons, 28.9% geneticists, 1.2% pathologists, and 9.6% other. If tested positive for a Lynch syndrome 57.3% suggest a yearly colonoscopy which should start at the age of 25 (47.9%). At the age of 35 and without diagnosis of colorectal cancer 40.9% would consider a purely prophylactic surgery. In case of a colon cancer at the age of 35 only 20.2% would opt for the standard oncological resection. 48.2% would opt for a subtotal colectomy and 28.9% for a total colectomy and ileorectal anastomosis. At diagnosis of rectal cancer 41.2% would opt for a standard oncological resection; 43.9% for a restaurative proctocolectomy A simultaneous prophylactic hysterectomy was chosen by 68.4% and a simultaneous oophorectomy by 53.5%. Chemoprevention with aspirin was attractive for 80.7% of the participants. 41.3% opting for100 mg, the rest for a higher dosage. 45.7% would start this chemoprevention between 20-29 years and 43.5% between 30-39 years. Conclusion: 40.9% of the participants would request a purely prophylactic surgery and in case of a colon cancer 80% would opt for prophylactically extended CR surgery. Experts prefer a more aggressive preventive approach than discussed in any guidelines worldwide.

G. Möslein1, C. Schneider1, R. Schneider2
1Department of General and Visceral Surgery, Bochum, Germany
2Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany

Purpose: Prophylactic proctocolectomy with an ileoanal J-pouch is the established procedure for patients with classic Familial Adenomatous Polyposis (FAP). In this series the functional outcome and QoL following construction of a shorter J-pouch limb of 8-9cm length were analyzed. Methodology: All patients with FAP who underwent hand-assisted laparoscopic proctocolectomy and small ileal pouch-anal anastomosis between 11/2005 and 01/2009 were retrospectively analyzed. Results: Out of 66 patients who underwent surgery 51 patients (77.3%) answered the questionnaire. 5 patients were excluded from this analysis, since they were secondary pouches. In 46/51 (90.2%) patients a pouch was conducted as a primary procedure and included in the study. The mean age at the time of surgery was 27.14±1.78 years. Mesenteric fibromatosis/desmoids tumour was detectable in 11/46 patients (23.9%) and suspected in 2/46 patients (4.3%). After a mean follow-up of 38.1±3.0 months 43/46 (93.5%) did not have incontinence, 3 patients (6.5%) reported incontinence during the night only. The mean stool frequency per day was 6.25±0.36. 32/46 patients (69.6%) quoted not to use any medication for stool regulation. Loperamide was used by 9/46 patients (19.6%) and expanding agents like Mucofalk were taken by 3/46 patients (6.5%). Both medications were used by 2/46 patients (4.3%). Conclusion: Smaller pouches perform equally when compared to larger pouches – both regarding functional results and QOL. Interestingly in this series a good functional result was achieved in a short time-period after ileostomy closure. The expected benefit in long-term outcome with less pouch-outlet problems is the focus of further follow-up of this series.

S. Nayagam, N. Muwanwella, N. Kelly, G. Forbes
Royal Perth Hospital, Perth, Western Australia, Australia

Infliximab (IFX) is known to cross the placenta during late second and third trimesters and is detectable in infants' sera for several months. There is currently limited data on the safety and efficacy of IFX during pregnancy, due to this it is often avoided in the third trimester. Retrospective analysis of hospital records of patients who received IFX for IBD during pregnancy at Royal Perth Hospital (2008-2011), was undertaken for treatment profile, maternal and fetal complications. Follow up phone interviews were then undertaken to assess child development and any medical issues in the first year of life. 5 patients with inflammatory bowel disease (IBD), all Crohn's disease, received IFX during the third trimester (mean age at delivery 26.2 years). Prior to pregnancy 4 were in remission on IFX, 1 was a new diagnosis during pregnancy. They received 3-6 doses of IFX during pregnancy, with the last dose at 32-36 weeks. Mean gestation was 38.5 weeks (national average 38.8 weeks). Delivery was uncomplicated in 3 patients (1 induced delivery due to poor disease control at 36 weeks, 1 emergency caesarean section due to pre-eclampsia at 37 weeks). Mean birthweight was 3.34kg (2.77-4.14kg, national average 3.37kg). There were no birth abnormalities, developmental delay or increased incidence of infections in the first year of life. In this small series of patients with difficult to control IBD, there were no adverse outcome to maternal, fetal or early childhood health following IFX therapy during the third trimester.

O.S. Omer, P. Cohen, S.F. Neong, G.V. Smith
Charing Cross Hospital, Imperial College Healthcare Trust, Fulham Palace Road, London, United Kingdom

We report the case of a 76 year old man who presented with moderate active Crohn's colitis refractory to high dose corticosteroids, mesalazine and 6-mercaptopurine. He received a trial of infliximab with poor response and was subsequently diagnosed with cytomegalovirus colitis, improving on antiviral therapy. Three weeks into treatment he developed acute respiratory distress with hypoxaemia and diffuse pulmonary interstitial infiltrates. This was confirmed as Pneucocystis jirovecii on bronchoalveolar lavage. He responded well to treatment with trimethoprim-sulfamethoxazole and was subsequently discharged home. It is unusual for human immunodeficiency virus (HIV)-negative patients to develop opportunistic infections following immunosuppressive therapy; however we have witnessed a rise in the number of cases since the advent of anti-TNF therapy. Our case raises the question of whether pneumocystis pneumonia (PCP) prophylaxis in inflammatory bowel disease (IBD) patients on immunosuppressive therapy is warranted? There is strong evidence that PCP in HIV-negative patients is diagnosed late and leads to severe respiratory distress associated with higher mortality rates. There are also suggestions that person-to-person transmission of P. jirovecii has the potential to cause disease outbreaks. Nevertheless, chemoprophylaxis against PCP in IBD remains a widely debated subject with contrasting recommendations from different governing bodies. This possibly relates to a lack of immune parameters to stratify patients according to risk of PCP. Clinical vigilance for PCP and awareness of the current consensus on PCP prophylaxis must be raised in order to drive research in this controversial area and ultimately lead to universal guidelines that take into account patient-dependent risk factors.

C.M.F. Pereira1, N.J. Veiga2, M. Baptista1, C. Chaves1, P. Nelas1,
M. Ferreira1, O. Amaral1, I. Coelho3 , J. Pereira1
1CI&DETS - Polytechnic Institute of Viseu, Portugal
2Health Sciences Department, Universidade Católica Portuguesa, Viseu, Portugal
3USF Grão Vasco, Viseu, Portugal

Background: Studies confirm that Helicobacter pylori (H. pylori) infection and dysfunctional dyspepsia may be a predisposing factor for gastric pathology later in life. The aim of this study was to estimate the prevalence of H. pylori and dysfunctional dyspepsia and analyze associated determinants in a portuguese sample of adolescents. Participants and Methods: A sample of 437 adolescents aged 12 to 18 years old, attending a public school in Sátão, Portugal, was enrolled in this cross-sectional study. A self-administered questionnaire was answered by the adolescents in classroom in order to assess socio-demographic aspects and dysfunctional dyspepsia was assessed by Rome III criteria. The adolescents were screened for H. pylori infection using the 13C-urea breath test that consists in the exhalation of carbon dioxide in samples before and after swallowing urea labeled with non-radioactive carbon-13. Prevalence was expressed in proportions and compared by the chi-square test. Crude odds ratio (OR) with 95% confidence intervals (CI) were used. Results: The prevalence of H. pylori infection was 35.9%. The H. pylori infection was associated with age (>15 years, OR=1.64 95%CI=1.1-2.52), residential area (rural, OR=1.48 95%CI=1.1-2.29), alcohol consumption (yes, OR=1.34 95%CI=1.2-2.20), soft drink consumption (yes, OR=0.62 95%CI=0.30-0.98). Dysfunctional dyspepsia was present in 22.4% of the sample and was associated with age (>15years, OR=2.24 95%CI=1.24-4.05), residential area (rural, OR=1.73 95%CI=1.05-3.39) and family history of gastric disease (yes, OR=2.84 95%CI=1.06-7.63). CONCLUSIONS: We found a high prevalence of H. pylori infection and dysfunctional dyspepsia among adolescents, suggesting that gastric pathology continues to be an important public health issue.

G.O. Patron1, D. Tello2, A. Roman3, E. Malaga3, V. Sanchez3,
F. Osorio3, M. Mieses3, F. Soria3
1Torrecardenas Hospital Almeria, Almeria, Spain
2Nuestra Senora del Prado Hospital Talavera de la Reyna, Toledo, Spain
3Maison de Sante Clinic, Lima, Peru

Clinical Case: A man of 35 year-old, diagnosed with hereditary angioedema (HA), admitted to the ER with nausea, vomiting and intense generalized abdominal pain, which got worse when breathing deeply. There was no visible sign of angioedema. His BP was 110/70 mmHg and his skin temperature was 36.1ºC (96.9ºF). Facing the possibility of an acute abdomen that would need surgery (i.e. acute appendicitis vs. bowel perforation), an abdominal echography was performed which showed moderate ascites while not being able to visualize the appendix. An abdominopelvic CT scan ruled out radiological signs of acute abdomen, the appendix was not visualized either, and no signs of chronic liver disease nor vascular alterations were detected; it only showed a moderate ascites. The patient was admitted into the GI unit for further studies, with only a symptomatic treatment. Forty-eight hours after his admission, the patient showed a marked improvement in his clinical as well as laboratory parameters. A control echography showed moderate ascites, and a normal portal vein and liver. Five days after the admission, the immunological studies showed low values of C4 and C1-INH(7.1 and 7 mg/dl respectively) and a C1q (17mg/dl) within the normality range. A diagnosis of abdominal crisis with moderate ascites due to type I HA was confirmed. Our allergology service prescribed a treatment with C1-INH (Berinert) at 20 UI/Kg for abdominal crises in the future.

G.O. Patron, B. Sierra, L. Moreno, A. Hernandez, R.A. Bendezu,
M.A. Rodriguez, S. Amat, A. Galvez, F. Anguita, F. Bravo, J.L. Vega, D. Tello |
Torrecardenas Hospital Almeria, Almeria, Spain

Objective: The long-term efficacy of ADA in patients with UC who have not previously responded to biological therapy. Methods: We conducted a retrospective study on a case series, between May 2008 and March 2012, of patients with UC who had previously failed IFX therapy and for whom compassionate use of ADA was prescribed; they were followed up to 144 weeks. Results: Of the total in the series, there were 5 women (83.3%) and 1 man (16.7%), the mean age being 52.6 years and the mean disease duration 8.17 years. Upon initiation of ADA therapy, 66.6% (4 out of 6 patients) had a Mayo score indicating severe flare-up and 33.4% (2 out of 6 cases) had a Mayo score indicating moderate flare-up. ADA therapy did achieve improvement in indicators and parameters of overall disease activity. Thus, in 66.6% of cases (4 out of the 6 patients), there was clinical and endoscopic improvement from week 48 until the end of the study (P=0.07). Likewise, PCR values had a tendency to decrease at week 48, in proportion to the clinical and endoscopic improvement; there was a statistically significant difference (P=0.046) between these values at the end of the study and those at the start of therapy. One of the 6 patients (16.7%) underwent surgery—subtotal colectomy due to a lack of response following intensification. By the end of the study, there had been only 1 case that, due to a loss of response to ADA, was transferred to the surgical unit.

G.O. Patron, R. A. Bendezu, M.A. Rodriguez, A. Hernandez, B. Sierra, L. Moreno, S. Amat, A. Galvez, F. Anguita,F. Bravo, J.L. Vega, D. Tello
Torrecardenas Hospital Almeria, Spain
OBJECTIVE: Retrospective evaluation of the long-term safety of ADA in patients with UC with previous Infliximab (IFX) failure. METHODS We conducted a retrospective study on a case series of patients with UC who had previously failed IFX therapy and for whom compassionate use of ADA was prescribed; they were followed up to 144 weeks. In all cases‚ there had been a previous trial of azathioprine (AZA) therapy, which was discontinued in 2 of the 6 cases (33.4%) due to adverse effects while 4 of them continued with this therapy. IFX was tried in the 6 cases, with no initial response and/or loss of response. The follow-up period was 144 weeks. In our study‚ the safety of ADA use was determined by the appearance of severe bacterial and viral infections, malignant neoplasms, and other complications. RESULTS: Of the total cases, there were 5 women (83.3%) and 1 man (16.7%). Induction therapy achieved an initial response in only 2 of the 6 cases (33.4%); in 4 of the 6 cases (66.6%) the therapy was intensified. At week 48 of the therapy, there was good clinical and endoscopic control in 5 of the 6 cases (83.3%). The most frequent infections were bacterial infections from common germs, with good response to empirical antibiotic therapy. There were 2 cases of cytomegalovirus (CMV) infection, which responded satisfactorily to ganciclovir. No cases of malignant

G.O. Patron, J.L. Vega Saez, A.G. Miras
Department of Gastroenterology Torrecardenas Hospital Almeria, Almeria, Spain

Objective: To determine the usefulness of the Blatchford score in non-varicose upper gastrointestinal bleeding as a predictor of emergency clinical and/or endoscopic intervention in our population. Materials and methods: Observational study that included 127 cases of upper gastrointestinal bleeding confirmed by endoscopy as high-risk according to the Blatchford score applied retrospectively. The study setting was the emergency department at Hospital Torrecardenas Almeria - Spain, between January 2010 and December 2011. Subjects were classified quantitatively into 2 high-risk subgroups according to the Blatchford score, group I less than 10 points and group II greater than or equal to 10 points, which was correlated with the need for emergency versus early clinical and endoscopic intervention. Preliminary Result: The most frequent endoscopic lesion for both subgroups is the type IIC based on the Forrest classification. Therefore, only 32.3% of cases required endoscopic sclerotherapy. 63% of cases received a blood transfusion due to acute anemia. This correlated significantly with a higher Blatchford score. The most frequent lesion in patients with a high-risk Blatchford score is Forrest IIC, with no significant difference in the high-risk subgroups. The need for blood transfusion is directly proportional to the high-risk Blatchford score.

R.S. Pinto, N.R. Kitteringham, C.E. Goldring, L. Kelly
The Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom

Paracetamol toxicity is the leading cause of acute liver failure in the United States and the United Kingdom. Much knowledge has been acquired about paracetamol metabolism through animal studies and some in vitro systems involving hepatoma cell lines are also beginning to emerge in the literature. However, there are many problems associated with the current models. This warrants further investigation into the development of an accurate cellular model for assessing the effects of paracetamol toxicity on hepatocytes. Here we present evidence that a novel model involving HepG2 cells incorporating a second-generation doxycycline-inducible gene expression system for CYP2E1 may be a useful in vitro system, in the assessment of paracetamol metabolism. Exposure of doxycycline induced HepG2 cells to increasing concentrations of paracetamol demonstrated glutathione (GSH) depletion, lactate dehydrogenase (LDH) release and reduction in adenosine triphosphate (ATP) production. However, several findings in this study suggest that paracetamol may play a role in toxicity prior to its oxidation to N-acetyl-p-benzoquinone imine (NAPQI). This model demonstrates important mechanisms involved in paracetamol toxicity consistent with known information acquired through animal models. Therefore this model may be useful in the further evaluation of paracetamol metabolism, and may also be used in the assessment of other CYP2E1 substrates as well as identifying novel targets for drug therapy in paracetamol toxicity.

M. Rivera1, C. Sers3, P.M. Schlag4, A. Schwan4, I. Fichtner1,
J. Hoffmann2
1Experimental Pharmacology, MDC-Berlin, Germany
2EPO GmbH, Berlin, Germany
3Institute for Molecular Pathology, Charite, Berlin, Germany
4Charite Comprehensive Cancer Center, Berlin Germany

Background: The EGFR has become one of the most interesting therapeutic targets in human colorectal carcinoma. KRAS mutations occurring in up to 40% of patients are exclusion criteria for EGFR-directed therapy and until now represent the only biomarkers that reached the clinic. However, among KRAS-wildtype patients only roughly 30% of the patients show a positive response and further reliable biomarkers are urgently needed. A training cohort of 29 colon carcinoma PDXs was extensively characterized regarding its sensitivity towards therapy and molecular characteristics with the aim to find predictive biomarkers. First correlation analyses suggest that the EGFR ligands amphiregulin and epiregulin are involved in resistance mechanisms towards EGFR-directed therapies. In order to validate these findings, a new cohort of PDX was established and characterized. Results: Samples from fresh, post operative colon carcinoma tissue from 39 patients were received and immediately transplanted subcutaneously to immunodeficient NSG mice. After three successful passages the model was established. The established xenograft tumors were characterized regarding their sensitivity towards classical cytostatic drugs and EGFR targeted therapeutics. In the study 16 out of 39 patient's samples engrafted and were characterized. The time for the primary engraftment ranged between four weeks and three months. The response rate of the tumors was heterogeneous and reflected well the clinical situation. Outlook: This newly established cohort of PDXs is being further characterized on the molecular level to assess the expression of EGFR and its ligands. This is aiming at further improvement of understanding EGFR function and resistance mechanisms towards substances targeting the EGFR. Furthermore, this well characterized xenograft cohort can be used for studies designed to test novel therapies for colon carcinoma or to improve existing ones.

A. Sano1, N. Tanigawa2
1Department of Radiology, Saiseikai-Izuo Hospital, Osaka, Japan
2Department of Radiology, Kansai Medical University, Osaka, Japan

PURPOSE: Sano, the presenter, have published case reports of portopulmonary venous anastomosis (PPVA) in patients with portal hypertension and esophageal varices, using portography and echocardiography. This is to show total 12 cases of PPVA with summarized radiologic features experienced in a single institution, and to overview on imaging of PPVA including portography, echocardiography, MDCT, or MRI. SUBJECTS & METHODS: Forty-six patients with esophageal varices undertook transhepatic portography, as well as cine-mode gastric venography by moving a fluoroscopic table top along the paraesophageal or mediastinal vein up to the superior mediastinum. RESULTS: Venographic motion pictures demonstrated dynamic flow patterns of PPVA in 12 out of 46 patients (26.1%), including left-sided PPVA in 9 (19.6%) and right-sided PPVA in 3 patients (6.5%). Venographic features showed a sudden spurt of the contrast medium from a mediastinal vein located near the lung hilus. Additional four-chamber view echocardiography demonstrated clouds of echoes in the left atrium after injecting 5% dextrose solution into the gastric vein in 5 patients, who accordingly showed PPVA on portographic motion picture, out of 15 patients studied (33.3%). DISCUSSION & CONCLUSION: Updated review of the literature suggests that MDCT and MRI have possibilities in recognition of PPVA before endoscopic sclerotherapy for patients with bleeding esophageal varices. As a matter of fact, there have been reports concerning complicated cerebral or systemic arterial embolism after the procedure. It should be taken into account that PPVA occurs more commonly than expected and intra-variceal sclerotherapy for bleeding esophageal varices is potentially hazardous.

N. Shemesh1, A. Leshno1, S. Shapira3, B. Schwartz2,
I. Naboishchikov3, S. Kraus3, N. Arber3
1Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, The Hebrew University of Jerusalem, Rehovot, Israel
2The Hebrew University of Jerusalem, Rehovot, Israel
3Integrated Cancer Prevention Center, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel

Introduction: Obesity is a global epidemic and it is a major risk factor for various health conditions including type II diabetes, cardiovascular disease and various types of cancer. Obesity is a multifactorial condition and it has genetic and environmental etiology. CD24 is a small heavily glycosylated glycosylphosphatidylinositol-linked cell surface protein that is expressed in a variety of cells- hematological, non-hematological and malignant cells. C248T polymorphism had been linked to colorectal cancer, lupus and multiple sclerosis. A recent study in CD24 knockout mice found that they were more obese as compared to wild type mice. Objective: The objective of our study was to test the hypothesis that C248T polymorphism is linked to obesity and metabolic syndrome variables in humans. Methods and participants: Our study included a group of 1932 participants. The participants were weighed and had blood collected for a genetic test of CD24 polymorphism. 3 variants were examined – CD24AA (WT), CD24 AV and CD24 vv. A subgroup of 256 participants also had blood collected for CRP, cholesterol, HDL-C, LDL-C and triglycerides. Results: Our study found that C248T polymorphism is not linked to obesity but it is linked to blood cholesterol levels. The difference in total cholesterol levels between CD24AA and CD24AV+VV was 21.28±8.75 mg/dl, p=0.041. Adjustment to gender showed a stronger link in women. The difference in total cholesterol in women between CD24AA and CD24vv was 48.12±16.85 mg/dl, p=0.014 and the difference between CD24AA and CD24AV was 51.15±17 mg/dl, p=0.009. The difference in LDL-C was 42.11±17.36 mg/dl, p=0.008 between CD24VVand CD24AA and 42.03±03±13.88 mg/dl, p=0.009 between CD24VV and CD24AV. Discussion: Our study found that C248T polymorphism is not linked to obesity but it is linked to blood cholesterol levels, especially in women. Our findings correlate with previous in vivo studies showing a link between CD24 and cellular cholesterol levels. The gender difference may be affected by hormonal dissimilarities since Estrogen has been found to suppress expression of CD24. Summary: We report that there is a link between C248T polymorphism and blood cholesterol levels, especially in women. More studies are required to further evaluate the outcome of these findings.

P.A. Soons2, C. Keung1, J. Biewenga2, B. Solanki1, G. Leitz1,
K. Lemmens2
1Janssen Research & Development, LLC, Raritan, New Jersey, United States of America
2Janssen Research & Development, Division of Janssen Pharmaceutica N.V., Beerse, Belgium

Background/Purpose: Epidemiological studies suggest a weak association of domperidone with serious cardiac adverse events, prompting a definitive ICH-E14 compliant QT/QTc study. Methods: Single-center, double-blind, 4-way crossover study in 44 healthy subjects randomized to 1 of 4 treatment sequences consisting of 4 treatment periods separated by 4-9 days washout. On day 1 of each 4-day period, participants began domperidone 10 mg or 20 mg qid, matching placebo qid, or single-dose moxifloxacin 400 mg (positive control)/placebo qid. In each period, triplicate 12-lead electrocardiograms were recorded at 8 timepoints during the first dosing interval on days 1 and 4 and predose on day 4. Baseline ECGs were recorded on day 1 at 30, 20, and 10 minutes predose. Difference between domperidone and placebo in least squares mean change from baseline for each day and timepoint and 90% CI were constructed using mixed effects models, with a prespecified clinically significant QTc change defined as >10 msec (upper limit, 90% CI). Results: Study-specific power was the optimal QT correction approach. Moxifloxacin response confirmed assay sensitivity. The largest mean difference of change from baseline versus placebo was 3.4 msec (20 mg qid, day 4), 90% CI: 1.0-5.9 msec, and <10 msec at all timepoints for both domperidone dosages. Participants achieved expected domperidone plasma exposures. Exposure-response analysis showed only 0.0619 ± 0.0571 msec QTc increase per ng/mL domperidone on day 4 (90% CI included zero at observed mean Cmax). Conclusions: Domperidone at doses up to 80 mg/day did not cause clinically relevant prolongation of the QTc interval.

G.J. Speight, N. Workman, P. Agashe, A. Smith, R. Stark,
A. Rogers, J. Anson
Oxford Gene Technology, Yarnton, Oxford, United Kingdom

Colorectal cancer (CRC) is the 3rd most common cancer, with >140,000 new cases estimated in the US for 2013. The 5-year survival rate at late disease stage is <10%, whereas the 5-year survival rate at early or pre-cancerous stages is >90%. Many countries are starting to employ screening approaches for those at highest risk (>60 years old). The most widely used screening tool is the faecal occult blood test (FOBt). A positive test directs patients for further clinical evaluation involving invasive tests such as colonoscopy. However, the presence of blood in the stool can be due to many factors. The poor positive predictive value of the FOBt leads to unnecessary concern for the patient, has associated morbidity effects, and has huge cost implications for the healthcare system. Consequently, there is a need for greater accuracy in the identification of appropriate patients for further clinical evaluation. Here we present data from a panel of 12 hypermethylated CpG island regions that have been successfully validated in tissue. A subset of this panel has previously been shown to have high sensitivity (94%) and specificity (98%) for carcinoma tissues, and, importantly, this performance is not eroded in tissue from pre-malignant adenoma samples (sensitivity 93%, specificity 98%). The areas under the ROC curves (AUC) were 0.984 for carcinomas and 0.968 for adenomas1. We have developed a multiplex qPCR-based method for the analysis of 12 markers using DNA from both blood and faecal samples. The application of this technology is described here.

J. Sperl1, S. Frankova1, V. Hejda2, M. Jirsa3, D. Merta4,
R. Bartakova1, P. Trunecka5, O. Viklicky6, J. Spicak1
1Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
2First Department of Internal Medicine, Medical school Plzen, Plzen, Czech Republic
3Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
4Department of Anesthesiology and Intensive Care Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
5Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
6Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

The treatment of HCV in hemodialysed (HD) patients remains controversial. HCV eradication improves long-term survival after kidney transplantation, but the treatment represents at least one-year delay of transplantation. In treatment strategy decisions, overall life expectancy as well as the probability of sustained virological response (SVR) achievement should be considered. The predictive factors of SVR in HD patients may differ from general HCV population. We evaluated 30 HD patients treated for chronic HCV, 21 males and 9 females, average age 51 years. All patients had genotype 1. The mean hemodiaysis period was 3 years (1-19 years). Pretreatment liver biopsy was performed in 28 patients, 8 of them had fibrosis stage 3 or 4. The IL28B genotype distribution was as follows: CC 33,3%, CT 60%, TT 6,7%. The mean initial viraemia was 9,3x10e5 IU/mL (1,2x10e1-7,2x10e6 IU/mL). All patients were treated with peginterferon alpha-2a and reduced ribavirin dose. The anticipated treatment period was 48 weeks. Twenty patients (66%) achieved an SVR. The planned 48-weeks treatment period was completed only in 18 patients, 12 patients stopped treatment prematurely due to adverse events. SVR achievement was associated with low initial viraemia (p= 0,0002), with rapid (p = 0,0001) and early (p = 0,0001) virological response (non-parametric Mann-Whitney test) and CC genotype IL28B (p=0,006) (Pearson Chi-square test). Age, sex, fibrosis stage and the HD duration did not influence the SVR achievement. Low pretreatment viraemia in HD patients predicts SVR achievement with higher reliability than the IL28B genotype in contrast to general population of HCV patients.

B. Tesfaye, J. Henry, S. Tammana, T. Cortni, A. Sanderson
Howard University Hospital, Washington, D.C., United States of America
Introduction: Spontaneous perforation of the small intestine is a well documented initial presentation or complication of Crohn's disease. Review of the literature shows that the most common site of free perforation is the ileum. Transmural inflammation of the intestinal walls makes them more susceptible to insult. Perforation of the jejunum as the initial presentation in Crohn's is rare and not well described in the literature. Our case brought to light an uncommon presentation of this disease. Case Report:: We report a case a previously healthy 34 year old Caucasian male who presented with a one day history of acute onset lower abdominal pain, nausea and vomiting. Abdominal exam revealed diffuse tenderness. CT abdomen and pelvis revealed bowel rupture with associated mesenteric inflammation, fecal matter, emphysema and adenopathy. The patient was taken for exploratory laparotomy. A perforated loop of jejunum was located eighty centimeters distal to the ligament of Treitz. Solid unmasticated mushrooms were found proximal to the perforation. The segment was resected and primary jejunal anastamosis was performed. Pathologic diagnosis of the resected bowel was Crohn's disease. Patient has a relatively benign post-operative course and initiated on therapy. Conclusion: Jejunal perforation as an initial presentation of Crohn's disease is very rare. In our patient emergency segmental bowel resection, primary anastomosis, and thorough washout resulted in a good outcome.

B. Tesfaye, J. Henry, F. Dejenie, S. Horton, A. Laiyemo
Howard University Hospital, Washington, D.C., United States of America

Introduction: Signet- ring carcinoma is uncommon in the small intestine, colon and rectum with reported incidence 0.1% to 0.9%.In the English medical literatures there are no reports of duodenal bulb signet cell carcinomas. Case Description: We describe a case of a 25-year-old Hispanic female who presented with abdominal pain, jaundice and weight loss of 4 weeks duration. She had icteric sclera and diffuses RUQ tenderness on physical exam. Laboratory values were notable for elevated liver enzymes, lipase and amylase levels. CT of abdomen and pelvis showed multiple liver lesions, left kidney hydroneprhrosis, dilated intrahepatic billiary ducts, ascites, lymphadenopathy, and bilateral ovarian mass. Biopsy of the ovarian mass revealed poorly differentiated mucinious adenocarcinoma with focal signet ring features. Immunostains revealed expression of CK7, CK20 and CDX2 which suggested a site of origin in the upper GI tract. Upper endoscopy revealed a mass arising from the duodenal bulb and obstructing the ampulla distally. No lesions were noted in the stomach. Colonoscopy revealed multiple masses throughout the large intestine. Biopsy of these masses also revealed poorly differentiated adenocarcinoma with focal signet ring features. The patient expired within a few days of admission before any therapeutic or palliative measures were initiated. Discussion: Our case is unique because of an unusual primary site and late presentation at a young age. The only case reported so far is in the Spanish medical literature of a 68 year old man who also presented at a late stage like our patient.

M. Toborek1, J.J. Choi1, S.Y. Eum1, E. Rampersaud2, M.T. Abreu3,
S. Daunert1
1Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida, United States of America
2John P. Hussman Institute for Human Genomics, University of Miami School of Medicine, Florida, United States of America
3Division of Gastroenterology, Department of Medicine, University of Miami School of Medicine, Florida, United States of America

Background: The gut microbiome is a dynamic bacterial community that interacts with the host and closely relates to human health by regulating energy metabolism and immune functions. Recent reports also point to the role of the gut microbiome in risk assessment to environmental toxicants. Objectives: To investigate the effects of polychlorinated biphenyls (PCBs) and exercise on the composition and structure of the gut microbiome. Methods: Mice exercised voluntarily for 5 weeks, followed by the exposure to a mixture of environmentally relevant PCB congeners (PCB153, PCB138 and PCB180; total PCB dose, 150 µmol/kg) for 48 h. The microbiome was assessed by determination of 16S rRNA. Results: Oral exposure to PCBs significantly altered the abundance of the gut microbiome in mice primarily by decreasing the levels of Proteobacteria. The activity level correlated with a substantial shift in abundance, biodiversity, and microbiome composition. Importantly, exercise attenuated PCB-induced changes in the gut microbiome. Conclusions: This study provides the first evidence that oral exposure to PCBs can induce substantial changes in the gut microbiome, which may then influence their systemic toxicity. Importantly, these changes can be attenuated by behavioral factors, such as voluntary exercise.

C. Ulrich1,2,3, N. Habermann1, E.C. Brown2, K. Buck1,
T.Y.D. Cheng2,3, K.W. Makar2,3, M.L. Neuhouser2,3, Y. Zheng2,
D.J. Duggan4, S.A. Beresford2,3 M. Wener5, H. Ochs-Balcom6,
A.T. Toriola7
1Department of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
2Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
3Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
4Translational Genomics Research Institutes, Phoenix, Arizona, United States of America
5Department of Laboratory Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America
6Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York, United States of America
7Division of Public Health Sciences, Department of Surgery and Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

Inflammation and angiogenesis are important pathways of colorectal carcinogenesis. Genetic polymorphisms in enzymes in these pathways may be associated with colorectal cancer (CRC) risk. From the Women's Health Initiative Observational Study of postmenopausal women aged 50-79 years, we selected 988 CRC cases and 988 matched controls (1993-2008). We genotyped 412 single nucleotide polymorphisms (SNPs) tagging 26 genes related to inflammation and angiogenesis (ALOX5, CRP, IL1B, IL6, PTGIS, PTGS1, PTGS2, TBXAS, TGFB1, TNF, ANGPT1, NGPT2, DKK4, DLL4, VEGFR1, IL10, KDR, MAPK1, NRP1, NRP2, PGF, IK3CA, PIK3CG, TEK, VEGFA) using the Illumina GoldenGate or Sequenom platforms. CRC risk was estimated by conditional logistic regression based on the co-dominant inheritance model (or dominant if allele frequency <10). P-values were adjusted for multiple comparisons using pACT. We report age-adjusted odds ratios (OR) and 95% confidence intervals (CI) among 821/821 Caucasians. SNPs in ALOX5 (rs1369214, rs2291427, rs7099684), NRP1 (rs7895812), PGF (rs174994), PIK3CG (rs12705393), PTGS1 (rs5794), TBXAS (rs1048766, rs12532529, rs2267680, rs41723, rs41728), and VEGFA (rs690001) were associated with CRC risk (p<0.05). Only the association with rs7895812 in NRP1 (neuropiline) remained significant after multiple comparison adjustment (OR=2.00 [95% CI=1.33-3.01] for GT/TT versus GG, pACT=0.02). This is the first study to date reporting a significant genetic association of a NRP1 SNP and CRC risk. VEGF are important angiogenic factors and neuropilin is a receptor for the specific isoform VEGF165. In previous studies, high levels of NRP1 were significantly associated with poor colon cancer outcome. The functional consequence of rs7895812 needs to be evaluated in future studies.

A.R. Valeeva1, K.H. Valeeva2, A. Abdulkhakov1, K.H. Odintsova3,
R. Abdulkhakov2
1Kazan State Medical University, Kazan, Russia
2Central Research Laboratory, Kazan, Russia
3Republican Clinical Hospital, Kazan, Russia

The aim of our study was to assess the amount of lipid peroxidation products and level of some cytokines in serum of patients with inflammatory bowel diseases (IBD). Methods: concentration of lipid peroxidation products (lipid hydroperoxides and malondialdehyde), ceruleoplasmin, tumor necrosis factor-alpha (TNF-alpha), interleukins 10 and 23 (IL-10, IL-23) was measured in serum of 52 patients with IBD (ulcerative colitis (UC) and Crohn's disease (CD)), 21 males and 31 females. Results: Lipid hydroperoxides' level was increased in 51 (98%) patients. The level of malondialdehyde was increased in 4 (7,7%) patients and decreased in 23 (44,23%) patients. The amount of ceruleoplasmin was elevated in 31,6% patients, including 67% patients with UC and 33 % patients with CD. It was also found that the level of TNF-alpha was increased in 24 (47%) patients, including 15 (62,5%) patients with UC and 9 (37%) patients with CD, and was within normal ranges in 28 (53%) patients. The level of IL-10 was increased in 45 (86,5%) patients and remained within normal levels in 7 (13,5%) patients. The amount of IL-23 was elevated in 90,7% patients with IBD. Conclusions: Increased levels of primary lipid peroxidation products, TNF-alpha, IL-10, IL-23 were observed in most of patients with UC and CD. What is more, these changes were detected more often in case of ulcerative colitis than Crohn's disease.


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