a cost-saving with “test and treat”, but a statistically significant difference was not detected,and any saving was balanced by the cost of “test and treat” over a one-year timeframe.

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Influence of PPI Run-in, pH Monitoring and Nutrient Tolerance On EfficacyOutcomes of Acotiamide Hydrochloride (YM443), a Novel AcetylcholineEsterase Inhibitor, in Functional DyspepsiaJan F. Tack, Nicholas J. Talley, Donna L. Kowalski, Mary Ann Borton, Abhijit Barve

Background: Functional dyspepsia (FD) is a highly prevalent condition with no effectivetherapy. Optimal study design, need for excluding concomitant heartburn and role ofsurrogate efficacy markers in FD trials have not been established. YM443 is a novel prokineticagent acting via acetylcholine esterase inhibition. Our aim was to evaluate the value of pHmonitoring, proton pump inhibitor (PPI) run-in and a liquid nutrient challenge in a doseranging trial of FD patients. Methods: Rome II positive FD patients enrolled in this double-blind, placebo-controlled 12 week trial went through a screening period with endoscopy,48-hour wireless esophageal pH monitoring and a liquid nutrient challenge test to determinemaximum tolerated volume (MTV), followed by a single blind 2 week PPI run-in (lansoprazole30mg daily) and 2 week washout, before being randomized to placebo (n=104), 300mg(n=103), 600mg (n=105) and 900mg (n=104), all TID. Primary endpoints were overall(adequate) relief of stomach symptoms in past 7 days (ORS, %) and overall treatmentevaluation past 7 days (OTE: 9 graded). Post-hoc, different time points, and response ratesaccording to results of pH monitoring and MTV were assessed. All analyses are on fullanalysis set; p values are 2-tailed. Results: Full analysis set included 404 subjects (70.5%female, mean age 43.3 yrs). pH monitoring was pathological (> than 4% time esophagealpH<4) in 39.9% patients. Response to PPI therapy occurred in 44 patients (5.4% of pH+ve and 3% of pH -ve) who were excluded from the randomization phase. Impaired nutrienttolerance (MTV<850 ml) was present in 315 patients (81%). Defining ORS responder asyes ≥50% weeks, the outcome is summarized in Table 1. Therapeutic gain was highest inthe first month. ORS at end of treatment was not significant and did not differ between pH+ve and pH -ve FD, while impaired MTV was associated with a higher response rate thannormal MTV. Similar findings were seen for OTE. Adverse events were minor and similaracross all arms. Conclusions: YM443 300mg is potentially beneficial in FD, especially inthe first month of treatment. The yield of a PPI run-in is low, and a nutrient challenge test,but not pH monitoring, might help predict responsiveness.Response Rate (%) of YM443 vs. Placebo for ORS

*P<0.05, **P<0.01, ^P<0.10

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Homozygous TRPV1 315C Influences the Susceptibility of Japanese People toFunctional DyspepsiaTomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Masakatsu Nakamura, HiroshiNakano, Ichiro Hirata

Background: The role of genetics in the susceptibility to functional dyspepsia (FD) is notwell established. Altered visceral sensation has been recognized as a pathogenesis of FD.Capsaicin/vanilloid (transient receptor potential vanilloid 1, TRPV1) receptor has been shownto be expressed in gastrointestinal tract and play a important role in human pain sensitivity.The G315C polymorphism affects the TRPV1 gene and alters its protein conformation. Aim:We aimed to clarify the association between TRPV1 G315C polymorphism and FD in aJapanese population. Method: 207 subjects (98 with no upper abdominal symptoms and109 with FD according to the Roma III criteria) enrolled in this study. We employed thePCR-SSCP method to detect the TRPV1 G315C polymorphism. H. pylori infection statuswas examined by histology or serum antibody against H. pylori. Results: In the non-dyspeptics,the TRPV1 genotype distribution was 23GG (23.5%), 46GC (46.9%), 29CC (29.6%). Mean-while, the TRPV1 genotype distribution in FD was 34GG (31.2%), 59 GC (54.1%), 16CC(14.7%). In over all subjects, the homozygous TRPV1 315C significantly decreased the riskof dyspepsia (CC versus others; OR = 0.41, 95% CI: 0.21-0.81) by Fisher's exact test. Thissignificant association remained after logistic regression analysis with adjustment for sexand age (OR = 0.41, 95% CI: 0.20-0.83). The same genotype also decreased risk of FDespecially in H. pylori positive subjects(OR = 0.25, 95% CI: 0.09-0.68) and both EPS (OR =0.38, 95% CI: 0.14-0.99) and PDS (OR = 0.30, 95% CI: 0.1-0.92) according to the RomaIII criteria. Conclusion: Our data suggest that the homozygous TRPV1 315C influences thesusceptibility of Japanese people to FD through altering the gastro duodenal sensation.

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Risk of Cervical Abnormalities in Women with IBD: A Population-BasedNested Case-Control StudyHarminder Singh, Alain Demers, Zoann Nugent, Salaheddin M. Mahmud, Erich V.Kliewer, Charles N. Bernstein

Two recent studies from tertiary care centers have reported an increased risk of cervicalcytological abnormalities in women with IBD. We evaluated the risk in a population-basednested case-control study. Methods: The source population was identified from the ManitobaCervical Cancer Screening Program database, which records all cytological and histologicalevaluations performed among Manitoba women aged 18 to 69 years. Women with abnormalpap smears or cervical biopsies (in situ and invasive cervical cancer, CIN I-III, ASC-H,ASCUS, LSIL, HSIL or AGC) were matched to 3 controls with normal Pap smears by yearof birth, year of first coverage in the provincial universal health care system, and numberof Pap smears in the preceding five years. All cases and controls had to be residents ofManitoba for at least five years prior to the index date and the control's normal Pap testhad to be reported in the same year the index case was diagnosed with abnormalities. Whenavailable, histological results were included instead of cytological results. Women with IBDwere identified using a previously validated case definition. An association with IBD wasassessed for all lesions collectively and separately for high risk lesions (in situ and invasivecervical cancer, CIN II, III, HSIL or ASC-H). Similar analyses were performed for exposureto immunosuppressant drugs (infliximab, methotrexate, azathioprine and 6-mercaptopurine)as determined from the comprehensive population-based provincial drug prescription data-base. Socio-economic status (SES) was determined by Socioeconomic Factor Index (SEFI).Odds Ratios (ORs) were estimated with conditional logistic regression analyses and wereadjusted for SES. Results: 31,656 women with cervical abnormalities were matched to 94,922controls. 987 women had IBD, including 264 who received immunosuppressants. Therewas no association between cervical abnormalities and IBD (OR 1.04, 95% CI: 0.90-1.20).Similarly, there was no association between high risk cervical abnormalities and IBD (OR1.12, 95% CI: 0.85-1.49). Women with IBD and taking immunosuppressants were not athigher risk of cervical abnormalities compared to those without IBD (OR for any cervicalabnormality 1.21, 95% CI: 0.92-1.60; OR for high risk cervical abnormalities 0.96, 95%CI: 0.54-1.72). Conclusions: These findings do not support an association between IBD orIBD treated by immunosuppressants and the risk of developing cervical abnormalities.

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Prevalence of Abnormal PAP Smears in Patients with Inflammatory BowelDisease On Immune Modulator TherapyThomas E. Lyles, Robert A. Oster, Alexandra Gutierrez

Background Human papillomavirus (HPV) subtypes (16, 18, 31, 35) are implicated in >95%of the genesis of cervical dysplasia (CD) and cervical cancer (CC). Multiple studies haveshown that immunomosuppressed patients such as renal transplant recipients and HIV/AIDS patients, have an impaired ability to clear virus, higher prevalence of HPV infection,and are at increased risk of CD and CC. Aim To investigate if immunomodulated (IM)inflammatory bowel disease (IBD) patients are at increased risk of developing squamousintraepithelial lesions (SIL) and CD. Patients & Methods Using ICD-9 codes, we identified1285 patients with a diagnosis of IBD seen at University of Alabama-Birmingham Hospitalbetween 1997-2007 and stratified them based on pap smear result at University Hospital;those without a pap smear were not analyzed. Patients diagnosed with CD or SIL wereclassified as cases and matched for years diagnosed with IBD and age. We recorded demo-graphic, laboratory, IM history (prednisone,azathioprine,6-MP,infliximab,cyclosporine,me-thotrexate), IBD and past medical history on all identified patients, aged 18-80. Baselinecharacteristics individually tested for differences between patients with and without thedevelopment of CD and CC. Comparisons between patient groups for continuous variableswere performed using the Wilcoxon rank-sum test and the two-group t test and comparisonsbetween for categorical variables were performed using Fisher's exact Results We identified51 patients (23 Crohn's disease, 28 Ulcerative Colitis) with abnormal pap smear and matchedwith 101 patients (55 Crohn's, 46 UC) with a normal pap smear. 51% of study patientshad history of IM, 86% had disease duration > 5 years, 57% had atypical squamous cellsof undetermined significance by pap, 29% had mild dysplasia, and 43% had evidence ofHPV infection. 81% of control patients had disease duration of greater than 5 years, andnone had an abnormal pap smear or evidence of HPV infection. Of the variables analyzed,number of concomitant autoimmune diseases (95% CI 1.0818, 5.8063 p=0.0254) wassignificant; azathioprine treatment duration (ATD) (p=0.0778) and concomitant STDs (p=0.0596) trended towards significance. Study patients tended to have a longer treatmentduration than controls. No statistically significant influence of age at diagnosis, IBD subtype,duration of disease, or other IM history (excepting ATD) on CD development. ConclusionIM treatment duration may be significant for the increase risk of development of CD andCC in IBD patients. Screening for concomitant STDs prior to initiation of IM therapy shouldbe standard to decrease the risk of development of CD and CC.

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Cervical Dysplasia and Inflammatory Bowel Disease: No Effect of DiseaseStatus or Immunosuppressants On Analysis of 2,199 Smear RecordsCharles W. Lees, Julia Critchley, Nellie M. Chee, Alan G. Shand, Ian D. Arnott, JackSatsangi

INTRODUCTION. It has been variously reported that there is an increase in cervical dysplasiaand neoplasia in women with inflammatory bowel disease (IBD) taking immunosuppressivetherapy (Kane et al, Am J Gastro 2007). However, this has not been studied in sufficientdetail for meaningful clinical interpretation. We therefore aimed to assess in a large, case-controlled population whether women with IBD had increased rates of abnormal cervicalsmears and whether there was any effect of immunosuppressive therapy or disease phenotype.METHODS. Women diagnosed with IBD prior to the age of 60 were identified from thepre-existing IBD database in Edinburgh. Full cervical smear histories were available on 411

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