vaccinated with PCV13 had, overall, a significant higher geometric mean (GM) post vaccina- tion antibody concentration than those vaccinated with PPV23 (PCV13 2.32 ±2.38; PPV23 1.53 ±1.69; p=0.02). Furthermore, when CD patients were stratified by treatment, vaccination with PCV13 resulted in a higher GM antibody response than vaccination with PPV23 in all groups (ID odds ratio (OR) 1.16, 95% CI 1.01-1.41; ID+TNF- α OR 1.17, 95% CI 0.76- 1.95; none OR 1.11, 95% CI 1.03-1.24). Vaccination with PCV13 in patients without immunosuppression resulted in a significantly higher GM value compared to any of the other groups, p<0.01. Conclusion PCV13 induced an overall higher antibody response than PPV23 when vaccinating CD patients. In addition, CD patients treated with ID alone or in combination with TNF- α had an impaired antibody response compared to patients not receiving any of these treatments. 927 End to End VS Side to Side Anastomosis and Post-Operative Crohn's Disease Quality of Life and Healthcare Utilization: A Prospective Comparative Effectiveness Study Mahesh Gajendran, Andrew R. Watson, Anthony J. Bauer, Claudia Ramos Rivers, Miguel Regueiro, Arthur Barrie, Jana G. Hashash, Leonard Baidoo, Marc Schwartz, Jason M. Swoger, David G. Binion INTRODUCTION: Anastomotic reconstruction following Crohn's disease (CD) surgery can employ end-to-end anastomosis (ETEA) which reconstructs the intestine as an intact tube or side-to-side anastomosis (STSA; i.e. "functional end-to-end") which transects circular muscle layers and has an anti-peristaltic orientation, creating a pouch like configuration at the anastomotic site. The CAST trial (McLeod RS et al. Dis Colon Rectum 2009) showed no difference in 30 day complications or endoscopic recurrence at 1 year between ETEA and STSA, but did not evaluate long-term patient centric measures including quality of life (QoL). We sought to compare ETEA vs. STSA in post-operative (post-op) CD patients beyond 1 year, focusing on QoL, clinical status and patterns of healthcare utilization. METHODS: This was a prospective observational study of post-op CD patients in a consented natural history registry who underwent 1 st or 2nd small bowel resection/re-anastomosis with 2 year follow-up. Patients were categorized as ETEA or STSA based on operative reports. Post-op QoL was assessed with short inflammatory bowel disease (SIBDQ) scores. Primary outcome variables were measures of clinical status - emergency department (ED) visits, hospitalizations, surgery, abdominal imaging and mean QoL scores. Secondary outcome variables were endoscopic recurrence, CRP levels and disease activity scores. RESULTS: 128 post-op CD patients (68 ETEA; 60 STSA) were included. There was no difference between ETEA and STSA groups regarding age, gender, active smoking, penetrating disease behavior, duration of CD, rates of laparoscopic surgery and use of post-op prophylaxis with immunomo- dulators and/or biologics (75% vs. 85.3%; p= 0.2). At 2 years post-op, ETEA patients had significantly lower rates of CT scans (13.2% vs.50%; p<0.001), MRI scans (0% vs. 10%; p= 0.009), ED visits (14% vs. 33%; p=0.013), hospitalizations (12% vs. 30%; p=0.01) and better QoL (mean SIBDQ 53.4 vs. 47.9; p=0.007) compared with STSA patients. There was no difference between ETEA and STSA patients regarding rates of overall post-op surgical procedures, repeat bowel resection, operative complications and secondary outcome variables. On multivariate analysis adjusting for smoking, penetrating behavior, history of resection and post-op prophylaxis, STSA had higher odds of hospitalization in the 2 year post-op period (OR 3.1, 95% CI 1.2-7.8) compared with ETEA. On linear regression after adjusting for penetrating behavior, history of resection and post-op prophylaxis, STSA and smoking were associated with lower mean SIBDQ scores of - 5.2 (CI -8.9 to -1.5) and - 10.1 (CI -14.6 to -5.6) respectively. CONCLUSION: STSA is associated with worse QoL and increased healthcare utilization in CD patients independent of inflammation, treatment and disease recurrence compared with ETEA during the 2 year post-op time period. 928 Double Blind Randomised Controlled Trial of Percutaneous Tibial Nerve Stimulation (PTNS) VS. Sham Electrical Stimulation in the Treatment of Faecal Incontinence Emma Horrocks, Stephen A. Bremner, Natasha Stevens, Christine Norton, Sandra Eldridge, Charles H. Knowles Background Percutaneous Tibial Nerve Stimulation (PTNS) is a relatively new ambulatory therapy for faecal incontinence (FI). Case series data suggest beneficial outcomes in 50-80% of patients however the outcome of PTNS vs. sham has not been trialled. We aimed to assess the short-term clinical efficacy of PTNS compared to sham electrical stimulation in adults with faecal incontinence. Methods In this multicentre, parallel-group, double-blind, randomised controlled trial involving 17 UK specialist centres, patients aged 18 years or over with significant faecal incontinence, who had failed conservative treatments were randomly assigned (1:1) to receive either PTNS or sham electrical stimulation. Randomisation was stratified by sex and then by centre in females. Patients and outcome assessors were masked to allocation for the 14-week duration of the trial when the effect of the intervention on severity of FI and quality of life was assessed using bowel diaries and validated questionnaires. A clinical response to treatment (primary outcome) was defined as a ≥50% reduction in weekly FI episodes. Secondary outcomes included reduction in mean weekly FI episodes, summative symptom scores, disease-specific and generic quality of life measures. ISRCTN registration number: 88559475. Results 227 patients were randomised (from 373 screened) to receive PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew; 7 from the PTNS group and 5 from the sham group. Missing data were multiply imputed. 39 patients in the PTNS group (38%) had a 50% or greater reduction in weekly FI episodes compared to 32 in the sham group (31%) (OR 1.28, 95% CI 0.72-2.28, p=0.396). There was a significantly greater decrease in mean total weekly FI episodes in the PTNS compared to sham group (difference in means -2.3, 95% CI (-4.2 to -0.3), p=0.02). This reflected a significant reduction in mean weekly urge (-1.5, 95% CI (-2.7 to -0.2), p=0.02) but not passive episodes (-0.64, 95% CI (-1.67 to 0.40), p=0.23). No significant difference in St Mark's Continence Score was observed between groups (difference in means -0.047, 95% CI (-1.033 to 0.939), p=0.93). No differences in the disease-specific Faecal Incontinence Quality of Life and Gastrointestinal Quality of life tools or the generic SF-36 quality of life S-177 AGA Abstracts tool were observed between the groups. No serious adverse events related to treatment were reported. Conclusions PTNS did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA Programme, NIHR, NHS or the Department of Health. 929 Age Related External Anal Sphincter Muscle Dysfunction and Fibrosis: Possible Role of Wnt Signaling Mahadevan R. Rajasekaran, Shantanu Sinha, Jay Parikh, Connie J. Oh, Ravinder K. Mittal, Valmik Bhargava Background and Aims: Studies show an age-related increase in the prevalence of anal incontinence (2.6% in adults and 15.3% in older population >70 years) and sphincter muscle atrophy 1, 2 . Wnt-β catenin signaling pathway is recently recognized as the major molecular pathway involved in age-related skeletal muscle atrophy and fibrosis 3 . The goals of our study were to evaluate: (i) impact of normal aging on the EAS muscle length-tension (L-T) function & morphology; and (ii) specifically examine the role of Wnt signaling pathways in anal sphincter muscle fibrosis during aging. Methods: New Zealand White female rabbits (six young 6 months old and six old 36 months of age (retired breeders) were anesthetized to study the L-T properties of the EAS. Anal canal pressure was measured using a 3 mm diameter sleeve sensor placed in custom designed probes of 4.5 mm, 6 mm and 9 mm diameter to determine the L- T function of EAS. Animals were sacrificed at the end of the study and anal canal was harvested and processed for histochemical studies (Masson trichrome stain for muscle /connective tissue and Sirius red for collagen) as well as for markers of Wnt signaling pathways ( β-catenin). Results: Significant L-T impairment was observed in older animals compared to the young ( Figure 1-A). Anal canal sections stained with trichrome showed a significant decrease in the muscle content (52% in old compared to 70% in young) and an associated increase in connective tissue/collagen content in the old animals (48% in old compared to 30% in young; Figure 1-B). An increased protein expression of β-catenin, a marker of Wnt signaling pathways was also seen in older animals ( Figure 1-C).Conclusions: Aging EAS muscle exhibits impairment of function and increase in connective tissue. Up regulation of Wnt signaling with aging may be the molecular mechanism for the age-related anal sphincter muscle dysfunction. References: 1. Lewicky-Gaupp C, Hamilton Q, Ashton- Miller J, Huebner M, DeLancey JO, Fenner DE. Anal sphincter structure and function relationships in aging and fecal incontinence. Am J Obstet Gynecol 2009;200:559 e1-5. 2. Whitehead WE, Borrud L, Goode PS, Meikle S, Mueller ER, Tuteja A, Weidner A, Weinstein M, Ye W. Fecal incontinence in US adults: epidemiology and risk factors. Gastroenterology 2009;137:512-7, 517 e1-2. 3. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 2007;317:807-10. 930 Is Rectal Hyposensitivity Caused by Bidirectional Gut and Brain Axis Dysfunction? Kulthep Rattanakovit, Askin Erdogan, Enrique Coss-Adame, Jigar Bhagatwala, Shaheen Hamdy, Satish S. Rao INTRODUCTION: Rectal Hyposensitivity (RH) is identified by increased rectal sensory thresholds to luminal stimulation and may cause constipation or fecal incontinence. It's underlying mechanism is unclear, in particular, whether the afferent or efferent gut and brain neurobiologic axis is dysfunctional. Moreover it remains uncertain if the abnormality is confined to the rectum or includes the anus. AIMS: To examine bidirectional anorectal- cortical axis in RH by assessing cortical evoked potentials (CEP) and transcranial magnetic stimulation-induced motor evoked potentials (MEP). METHODS: 58 consecutive RH patients with chronic constipation (Rome III) and 24 healthy controls were enrolled. CEPs were assessed by electrical stimulation of anus and rectum with a probe containing 2 pairs of bipolar steel ring electrodes, each 2 cm apart. Anal and rectal MEPs were assessed by the same probe following TMS with a magnetic coil (Magstim, UK) placed over the right and left paramedian cortex. Stimulation intensity was between 50-90% (maximum 2 Tesla). Sensory thresholds for first sensation and pain, latencies (P1, N1, P2, N2) and amplitudes (P1-N1, P2-N2) for rectal and anal CEPs, and bilateral latencies and amplitudes for rectal and anal MEPs were analyzed and compared. RESULTS: Electrosensory thresholds (in mA) for first sensation and pain in RH patients were significantly higher (p < 0.0001) than controls in rectum (35.6 ± 3.3 and 75.5 ± 3.8 vs 19.2 ± 2.0 and 47.4 ± 4.6 respectively) and anus (18.7 ± 2.5 and 53.93 ± 4.6 vs 9.0 ± 1.2 and 36.4 ± 3.5 respectively). Both rectal and anal CEP latencies (P1 and N1) were significantly longer (p < 0.0009) in RH subjects compared to controls (Table 1). Anal CEP amplitudes (P1-N1) were also lower (p < 0.03) compared to controls. Bilateral rectal and anal latencies for MEP responses (Table 2) were significantly prolonged (p < .0.0005), but amplitudes were larger (p < 0.008). CONCLU- SION: Rectal hyposensitivity is characterized by delayed nerve conduction between the ascending anorectal-cortical axis as well as the descending cortical-anorectal axis. Thus, bidirectional neuronal transmission is abnormal in RH, indicating not only afferent but also efferent neuropathy. Furthermore, it affects both the rectum and anus. The increased anorectal MEP amplitudes in RH subjects may represent a compensatory motor adaptation to sensory impairment. Acknowledgement: NIH Grant RO1-DK057100-06A. AGA Abstracts