T1032 Patients with Functional Gastro-Intestinal Disorders May Be Exposed to Significant Amounts of Medical Radiation.

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retrospective analysis. All 12 patients (100%) responded immediately to treatment and reported marked resolution of constipation. 11/12 patients (91.7%) maintained resolution of constipation over the follow-up period (1-18 months) with only 1 patient reporting recurrence after 10 months. 11/11 patients with long-term resolution had a pre-treatment stool frequency of 0-4 times per week which improved to 1-3 per day with treatment. 10/ 11 patients reported hard or lumpy stools (Bristol Stool Chart4 type of 1-2) before treatment, which improved to “normal” or soft stools (type 3-5) with treatment. The final patient with occasional alternating constipation and diarrhea was consistently “normal” with treatment. Complete resolution of associated symptoms was reported by 9/11 patients (81.8%) and the remaining 2 patients (18.2%) reported either resolution or improvement of individual symptoms. Conclusions: 1. Colchicine/olsalazine combination markedly improved constipation in 91.7% of patients treated. 2. This therapy resolved associated symptoms in 81.8% of these patients and improved symptoms in the remaining 18.2%. 3. Colchicine with olsalazine is an effective treatment for IBS-C. References: 1. Camilleri M et al. Aliment Pharmacol Ther 1997;11:3-15. 2. Lesbros-Pantoflickova D et al. Aliment Pharmacol Ther 2004;20:1253-96. 3. Camilleri M et al. Aliment Pharmacol Ther 2002;16:1407-30. 4. Lewis SJ et al. Scand J Gastroenterol 1997;32(9):920-4.

AGA Abstracts

High-Frequency Gastric Electrical Stimulation for the Treatment of Gastroparesis: A Meta-Analysis Gregory O'Grady, John U. Egbuji, Peng Du, Leo K. Cheng, Andrew J. Pullan, John A. Windsor Background & Aims: High-frequency gastric electrical stimulation (GES) is a relatively new treatment for medically-refractory gastroparesis. A commercial device is available (Enterra, Medtronic, Minneapolis), and a number of clinical studies have been published reporting the efficacy of this treatment. A systematic review and meta-analysis was performed to evaluate the evidence for improved clinical outcome. Methods: A literature search of major medical databases was performed for the period January 1992 to August 2008. Clinical studies involving an implanted high-frequency GES device were included and a range of clinical outcomes were evaluated. Studies of external, temporary and/or low frequency GES were excluded. Because of a paucity of controlled trials, non-controlled clinical trials were also included for analysis. Results: Of the 26 studies located, 13 were accepted for inclusion. Of these studies, 12 lacked controls and only one was blinded and randomized. Following GES, patients reported improvements in total symptom severity score (3/13 studies, mean difference 6.52 [CI: 1.32, 11.73], p=0.01), vomiting severity score (4/13, 1.45 [CI: 0.99, 1.91], p<0.0001), nausea severity score (4/13, 1.69 [CI: 1.26, 2.12], p<0.0001), SF-36 physical composite score (4/13, 8.05 [CI: 5.01, 11.10], p<0.0001), SF-36 mental composite score (4/13, 8.16 [CI: 4.85, 11.47], p<0.0001), requirement for enteral or parenteral nutrition (8/13, OR 5.53 [CI: 2.75, 11.13], p<0.001) and 4-hour gastric emptying (5/13, mean improvement 12.7% [CI: 9.8, 15.6], p<0.0001). Weight gain following stimulation did not reach significance (3/13, 3.68kg [CI: -0.23, 7.58], p=0.07). The device removal or reimplantation rate was 8.3%, primarily due to infection (3%) or problems occurring at the site of implantation (4.9%). Conclusions This systematic review, of the best available evidence, finds significant and clinically important benefits for high-frequency GES in the treatment of medically-refractory gastroparesis. However, caution is necessary in interpreting the results, primarily due to the limitations of uncontrolled studies. Further controlled studies are required to confirm the clinical benefits of high-frequency GES. Results here provide strong grounds for the further development and evaluation of high-frequency GES.

T1031 Reliability of ROME III Criteria in Characterising IBS in Chronic Constipation. An Audit of Patients Attending a Specialist Clinic Usman Khan, Tony Hildreth, Jag Varma, Yan Yiannakou Introduction The recently revised ROME III criteria characterise chronic constipation into either Constipation predominant Irritable Bowel Syndrome (IBS-C) or Functional Constipation (FC)[1]. Validation of these criteria has been mainly in diarrhoea predominant IBS, and their usefulness in clinical practice is uncertain. We performed an audit to test the reliability of our diagnoses using ROME III criteria. Methods A convenience sample of stable follow-up patients attending a specialist constipation clinic answered self-administered ROME III questionnaires (SAQ) for characterising IBS. In these patients a diagnosis of chronic constipation had previously been made using physician administered ROME III questionnaire (PAQ). The two assessments were within six months of each other in all cases. These questions covered; duration and frequency of pain, improvement in pain after defecation, change in frequency of stools since the onset of pain and change in form or appearance of stools since the onset of pain. Inter-observer agreement was calculated using weighted kappa coefficient (k) and Wilcoxon signed ranks test was used to calculate differences. Results 64 patients were studied (55 F, 9M). IBS-C was diagnosed in 38 (60%) patients using SAQ, and 17 (27%) patients according to the PAQ (k= 0.22,95% CI 0.04 to 0.41). There was good agreement between SAQ and PAQ relating to onset and duration of pain. The discrepancy between SAQ and PAQ was due to differences in answers relating to frequency and the appearance of stools since the onset of the pain (k in table 1). Wilcoxon signed ranks test was significant (p value <0.05) for these factors. Conclusions We found significant incongruity between patients and physicians for characterising IBS according to ROME III criteria in this patient population. This could be because patients or physicians find some ambiguity in the questions, or possibly because of changes over time in our patient group. A formal research study is needed for further clarification. References: 1.Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC, ROME III criteria for functional constipation. Gastroenterology 2006; 130:1480-1491 Agreement between patient and physician administered ROME III questionnaires for IBS

T1029 Lack of Utility of Lactulose Breath Testing in the Irritable Bowel Syndrome (IBS) Davinder K. Sandhu, Nicholas J. Talley, G. Richard Locke, Alan R. Zinsmeister, Rodney Sandberg, Yuri A. Saito Background: Small intestinal bacterial overgrowth (SIBO) is a condition in which the relatively sterile small bowel contains excessive colonic-type bacteria. The current gold-standard for diagnosis is aspirate culture, but the diagnosis can be suggested non-invasively by lactulose breath testing (LBT). Much interest has focused on the role of SIBO in the development of IBS as measured by the LBT, and further investigation of this relationship is warranted. Aims: To estimate the potential proportion of patients with SIBO among patients who underwent LBT at Mayo Clinic Rochester in a two-year period and to identify the clinical predictors of a positive LBT. Methods: A retrospective chart review was performed of all patients who underwent lactulose hydrogen/methane breath testing at Mayo Clinic Rochester from June 2006 to June 2008 using a standard protocol with 50g of lactulose. Data on indication for testing, clinical diagnoses, GI symptoms, medications, and LBT results were collected. A positive result was defined as: 1) a biphasic peak, 2) rise in hydrogen levels >12 in 60 min, 3) rise in methane levels >12 in 60 min, or 4) high baseline methane level >20ppm. The proportion and 95% CIs of positive results was estimated overall, as well as in those with IBS. Univariate and multivariable logistic regression analysis were used to identify clinical features that predicted the LBT results. Results: 253 patients were identified. Median age was 53 (range 18.9-89.6) and were 70% female. The primary indication for testing was diarrhea (46%), and 55 (22%) had a final diagnosis of IBS. In the entire sample, 74 (29%[95%CI:23.8-38.4]) had a positive test suggestive of SIBO; of the 55 IBS patients, 17 (31%) had a positive test, while 30% of the 196 without IBS had a positive test(p=0.79). Variables univariately associated with a positive test included older age(p=0.03) and bloating (p=0.04). Neither IBS, IBS symptoms, nor specific medications were predictors of a positive LBT. In a multiple variable regression model including age (OR 1.02, p=0.01), gender (OR 0.72, p=0.29), IBS diagnosis (OR1.09, p=0.33), PPI use (OR 0.98, p=0.95), and narcotic use (OR 0.44, p=0.065), only older age was significantly associated with positive LBT. Conclusion: Only a minority of subjects with diarrhea and specifically IBS, had a positive LBT result suggestive of SIBO, with bloating being the only clinical predictor of a positive LBT. No other symptoms, medications, or an IBS diagnosis were identified as clinical predictors of a positive test. Our comprehensive chart review of hydrogen and methane testing suggests that lactulose breath testing has no utility in patients with IBS.

T1032 Patients with Functional Gastro-Intestinal Disorders May Be Exposed to Significant Amounts of Medical Radiation. Alan N. Desmond, Kevin N. O'Regan, Katie Walsh, Sebastian McWilliams, Michael M. Maher, Fergus Shanahan, Eamonn M. Quigley AIMS: Exposure to ionising radiation may be associated with increased risk of malignancy. We (Desmond AN et al. Gut 2008; 57: 1524-29) and others have previously reported significant cumulative exposure to medical radiation in patients with inflammatory bowel disease (IBD). We now describe imaging trends and cumulative effective dose (CED) of medical radiation among out-patients referred to a tertiary centre gastroenterology clinic with a special interest in functional gastrointestinal disorders (FGIDs). METHODS: A total 1909 patients were referred to the FGID clinic for assessment between January 1999 and November 2008 (1161 female, 749 male; mean age 41.7 yrs, age range 3 months - 89.2 years; mean follow-up 1 year, range 0 - 9.3 years). Of these, 372 patients (19.5%) were diagnosed with an FGID alone. Other diagnostic groups were: IBD (n=84); other gastro-intestinal (GI) diagnosis (n= 1016); no GI diagnosis, (n=420); and malignancy (n=17). CED was calculated retrospectively from all medical imaging performed during the 9.9 year study period. RESULTS: A total 8390 imaging studies were performed (4820 plain radiology, 1181 computed tomography, 1028 ultrasound, 556 barium studies, 275 interventional, 241 nuclear medicine and 289 others). 61.2% of patients underwent some form of imaging. The population was exposed to a total 14774 milli-Sieverts (mSv) of medical radiation, of which 59.6% (8762 mSv) occurred within 12 months of GI clinic attendance. 66.1% of radiation exposure (9764 mSv) was due to abdomino-pelvic imaging. Mean CED per patient imaged was 12.6 mSv (range 0 - 189 mSv). CED exceeded 25 mSv in 3.8% of all patients (n=73) and was >50 mSv in 2.5% of cases (n=48). Computed tomography accounted for 14.1% of studies and 48.8% of medical radiation. Mean CED (and 95% CI) among diagnostic groups was as follows: FGID only, 5.4 mSv (4.4 - 6.4); IBD, 13 mSv (7.5 - 18.5); other GI diagnosis, 7.1

T1030 Colchicine Plus Olsalazine for Treatment of Constipation-Predominant Irritable Bowel Syndrome Thomas J. Borody, Lauren A. Hills, Margaux Torres Irritable Bowel Syndrome (IBS) affects approximately 10-15% of the Western population.1 Treatment is generally focused on alleviating the patient's specific predominant symptom2 and traditional therapies have shown limited or no efficacy.2,3 A novel combination of colchicine and olsalazine has shown promise in the treatment of constipation-predominant IBS (IBS-C). Aim: To report a single centre experience with colchicine/olsalazine combination in the treatment of IBS-C and its associated symptoms. Methods: Patients with constipation and associated symptoms (abdominal pain, bloating, straining, fatigue, flatulence, and sensation of incomplete evacuation) were treated with ramping-up doses of olsalazine and colchicine. Olsalazine dose began at 250 mg/d and increased by 500mg/d to reach a maximum of 1500mg/d. Colchicine began at a dose of 500 mcg/d and progressively reached a dose of 1000-2000 mcg/d. Results: 12 patients (1M, 11F; aged 23-75y) were included in this

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mSv (6.2 - 8.1); no GI diagnosis, 8.0 mSv (6.1 - 9.9) and; malignancy, 21.3 mSv (8.4 34.2). Mean CED was not significantly different between the non-malignancy diagnostic groups. CONCLUSION: Patients with functional gastro-intestinal disorders frequently required radiological studies and were exposed to significant levels of medical radiation which were comparable to levels for patients with so-called “organic” GI disorders. Our results, and previously published findings, call for the development of low-radiation protocols for patients who require abdomino-pelvic imaging.

T1035

Background Alanine transaminase (ALT) levels are widely used in screening for liver disease. The upper limit of normal (ULN) of ALT (males 30 IU/l, females 19 IU/l) have been defined for western populations. Normal levels have not been established for Asian populations. Objectives To establish levels of ALT for a normal, adult Sri Lankan population Methods This study was part of a community based investigation - Ragama Health Study (RHS). The study population consisted of 35-64 year old adults, selected using stratified random sampling. Consenting adults were screened by a structured interview, liver ultrasound and collection of 10 ml venous blood. The “normal” population was defined as those not using potentially hepatotoxic drugs, safe alcohol consumption (14 units/week for males, 7 units/ week for females), absence of fatty liver, and being HBsAg and anti-HCVab negative. ALT levels were estimated by a kit using the Bergmeyer method. The 95th percentile of the ALT levels was taken as the ULN. Results 3012 subjects participated in the study. The ALT level (U/l) among 831 normal males (mean 36, median 30, SD 20, ULN 68) was significantly higher than that of the 885 normal females (mean 29, median 25, SD 13, ULN 53) (p<0.001, Student's t-test ). Conclusion The ULN for ALT levels of a “normal” Sri Lankan population was higher than observed in western populations. The levels were higher in males. ULN for ALT may need to be redefined for different population groups.

T1033 Health-Related Quality of Life Associated with Chronic Constipation or Irritable Bowel Syndrome with Constipation Yaping Xu, Karen Lasch, Samuel Wagner, Jonathan Chapnick, Omar Dabbous Introduction: Chronic constipation (CC) and Irritable Bowel Syndrome with constipation (IBS-C) can negatively affect health-related quality of life (HRQoL). The objective of this study was to evaluate the effects of CC and IBS-C on HRQoL, by using a sample of subjects from the National Health and Wellness Survey (NHWS) conducted by Consumer Health Sciences International. Methods: Data were taken from the 2007 U.S. NHWS database, an annual cross-sectional internet survey of the healthcare attitudes and behaviors of adults (aged ≥18 years). Respondents indicated whether they suffered from CC or IBS-C in the past 12 months, and were then directed to answer a series of questions about the conditions. Respondents with CC or IBS-C were then compared to a control group of respondents without the conditions. HRQoL data were collected by using the validated instrument, SF12v2, and both mental and physical component summary scores were computed, which are normative to the US population (mean score=50, SD=10). Higher scores indicated better physical or mental well-being. A difference of 3 to 5 in the component scores were considered clinically meaningful. Multivariate linear regression models were developed to adjust for potentials confounders including demographics, psychiatric illness, other GI diseases, cancer, opioid use, body weight, the status of alcohol use, smoking, and exercise, and comorbid conditions. Results: Among the 63,012 respondents in the survey, there were 2,648 subjects with CC or IBS-C, and 60,364 controls. Females comprised 67% of the CC or IBS-C subjects (vs. 50% for controls), and the mean age was 49.4 years (47.8 years for controls). Compared to the control group, subjects with CC or IBS-C were more likely to smoke (64% vs. 55%, p<0.05), less likely to use alcohol (60% vs. 67%, p<0.05), and exercised less (5.8 days/ month vs. 7 days/month, p<0.05). The CC or IBS-C group had significantly worse mean physical (38.5 versus 47.6, p<0.05) and mental (40.9 versus 48.1, p<0.05) scores than controls. After adjusting for the confounders listed above, CC or IBS-C subjects had significantly lower physical (3.1, p<0.001) and mental (2.4, p<0.001) scores than the control group. Conclusion: CC and IBS-C are associated with a significant negative effect on physical and mental quality of life. Treatments that alleviate the symptoms of CC or IBS-C may prevent worsening of HRQoL, thereby alleviating the significant burden of this illness. Further studies are warranted to validate study findings.

T1036 Clinical and Laboratory Features of Patients with Significantly Elevated Serum Gastrin Level Gokhan Kabacam, Mehmet Bektas, Yusuf Ustun, Mustafa Yakut, Murat Toruner, Hulya Cetinkaya, Irfan Soykan Background: The most frequent conditions of hypergastrinemia are the Zollinger-Ellison syndrome (ZES) and type A autoimmune chronic atrophic gastritis. It has been reported that, a fasting serum gastrin level greater than 1000 pg/mL is virtually diagnostic of ZES. Methods: The aim of this study was to investigate the clinical and laboratory features of patients (pts) with significantly elevated (>1000 pg/mL) serum gastrin level. Fifty-two pts (34 women, median age: 53 yrs) with various gastrointestinal (GI) complaints with significantly high serum gastrin level (35 pts: > 1000 pg/mL, 17 pts: 500-1000 pg/mL) were included into the study. Pts were evaluated in terms of GI symptoms, upper GI endoscopy+biopsy, gastric juice pH, antiparietal cell antibody (APCA) presence of Helicobacter pylori, and serum iron and vitamin B12 level. Results: The median fasting gastrin level in 52 pts was 1596 pg/mL. The main symptoms of pts were: bloating=14, epigastric pain and diarrhea=8, abdominal pain=7, intermittent diarrhea=4, fatigue=8, amnesia=5, nausea=6, referred for vitamin B12 and iron deficiency=6, heartburn=3, chest pain=4, and gnawing= 1 . All pts were negative for Helicobacter pylori. The mean gastric juice pH was 6.5. Twentysix pts' vitamin B12 level were under normal range (<160 pg/mL). There was no relationship between gastrin and vitamin B12 level (r=-0.058, p=0.687). Fourteen pts (27%) had various thyroid diseases (Hashimoto's thyroiditis=10, Graves=2, nodular thyroid disease=2), 6 had diabetes mellitus and 2 pts had biopsy proven steatohepatitis. All pts (n=10) who had Hashimoto's thyroiditis exhibited serum gastrin level over 1000 pg/mL (r=0.275, p<0.05). The final diagnosis of 52 pts was autoimmune gastritis (AIG) in 50 (96%), ZES and retained antrum in two pts. In 50 pts with AIG, 3 of them also had gastric carcinoid type I, and one patient had gastric antral vascular ectasia. Endoscopic findings revealed fundic gland polyposis in two pts and gastric hyperplastic polyps in another two pts. APCA was studied in 38 pts with AIG and 32 (84%) of them were positive for APCA. Conclusions: Most of the pts with serum gastrin level over 1000 pg/mL have AIG and negative for Helicobacter pylori infection. The prominent symptoms of these pts were abdominal bloating and epigastric pain+intermittant diarrhea. Patients with auotimmune thyroid disease should also be screened for the presence of AIG. Gastric juice pH determination and histopathological examination of the gastric corpus biopsies should be the initial steps for the investigation of elevated serum gastrin level before initiating expensive tests such as octroscan or endoscopic ultrasonography.

T1034 Symptom Severity, Quality of Life and Associated Factors in Patients with Irritable Bowel Syndrome Managed in Primary Care Roger Jones, Claire L. Hunt, Jonathan Blanchard Smith, A. A. Hungin Introduction: Most patients with irritable bowel syndrome (IBS) are managed in primary care, but little information is available about symptom control, quality of life and other aspects of their well being. Objective: To document details of the care of patients with IBS in general practice in the UK in relation to symptom status, quality of life and a range of psychological parameters. Methods: Patients under treatment for IBS by 37 family practitioners in 5 primary care centres in the UK who had consented to take part in a quality improvement project completed survey instruments,on symptom severity (IBS SSS), quality of life (IBS-QOL and EQ5D), anxiety and depression (HADS) patient enablement (Patient Enablement Instrument, PEI) and patient satisfaction (General Practice Assessment of Quality consultation subscale, GPAQ). Results: We studied 219 patients, of whom 162 (74%) were female; mean age 53 years (range 21-86), with a mean duration of IBS of 5.3 years (range 0-50). The mean primary care consultation rate amongst those who had consulted in the previous 12 months was 3/year (range 1-25); 39% (81/206) of patients had not consulted for their IBS, and only 9% (19/210) had visited a gastroenterologist in the last year (mean of 2.6 consultations; range 1-12). Only 6% reported seeking advice from a complementary therapist and 3% had been treated with a psychological therapy for IBS. The mean IBS SSS score was 232.6 ± 83, indicating that 80% of patients had mild or moderate disease and 20% were classified as still having severe disease. There was a significant effect of symptom severity on the performance of usual activities (χ2=6.188, p=0.045) and pain or discomfort (χ2=15.676, p<0.0005) sub scales of the EQ5D. The population mean for the IBS QOL was 72.3 ± 21.4, and for the EQ5D 71.4 ± 17.7 respectively: There were significant negative correlations between symptom severity scores and IBS-QOL (r=-0.710, p<0.0005), and EQ5D scores (r=-0.374, p<0.0005). Increasing symptom severity was associated with persisting anxiety (r=0.457, p<0.0005), and depression(r=0.357, p<0.0005), and was inversely correlated with patients' scores on communication with their primary care physicians (r=0.258, p<0.05) but not with patient enablement. Borderline or definite anxiety was identified on the HADS as being present in 51% of patients. Comment: There is persisting impairment of quality of life, persisting symptoms and continuing psychological problems in a representative IBS population managed in primary care in the UK. Current management strategies fall short of providing an adequate degree of symptom relief and restoration of quality of life.

T1037 Response-Guided Therapy of Peginterferon Alpha 2B Plus Ribavirin for Chronic Hepatitis C with Genotype 2 and a High Viral Road As An Effective Method Optimizing Therapy Duration Ken Sato, Katsuhiko Horiuchi, Atsushi Naganuma, Takashi Kosone, Kazuhisa Yuasa, Hiroki Tahara, Mitsuo Toyoda, Satoshi Hagiwara, Hiroki Tojima, Takeshi Ichikawa, Satoru Kakizaki, Hitoshi Takagi, Masatomo Mori Background: The sustained virological response (SVR) rate in patients infected with hepatitis C virus (HCV) is reported to be closely associated with rapid virological response (RVR; HCV RNA level <50 IU/mL at week 4) of therapy with pegylated interferon (peginterferon) alfa-2b plus ribavirin. Patients infected with HCV genotype 2 and a high viral road have SVR rates of approximately 70-80% after 24-week peginterferon plus ribavirin therapy. Aim: We conducted a prospective study to optimize the therapy duration of peginterferon alfa2b plus ribavirin therapy based on virological response at week 2 and 4 after receiving therapy. Patients and Methods: A total 65 study subjects with HCV genotype 2 and a high viral road have received peginterferon alfa-2b 1.5μg/kg/week plus ribavirin based on body weight daily. The therapy duration was assigned to be 12 weeks in patients achieving super rapid virological response (HCV RNA level <50 IU/mL at week 2), 24 weeks in patients achieving RVR, and 48 weeks in patients showing late virological response (HCV RNA level≧50IU/mL at week 4). A SVR was defined as an undetectable serum HCV RNA level (<50 IU/mL) 24 weeks after the end of therapy. Results: The overall SVR rate was 73.8% (48/65) comparable to the established reports. The SVR rate was 75% (6/8), 75% (36/48), and 66.7% (6/9) in super rapid virological response group, RVR group, and late virological response group, respectively. The patients that did not agree with the study protocol and showed late virological response revealed only 26.7% (4/15) of the SVR rate for 24-week

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Alanine Transaminase (ALT) Levels in Normal Adult Sri Lankans M. A. Niriella, A. S. Dassanayake, K.Kalubowila U. Kalubowila, Arjuna P. De Silva, Ananda R. Wickremasinghe, N. Kato, M. Makaya, H. J. de Silva