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sloss of stool” as their sole reason, contradicting their answer on the e-PAQ -PF. The mostfrequently cited reasons for not discussing FI were “other health problems more importantto discuss”(n=9), “able to manage symptoms on my own”(n=7), and “thought leakage wasa normal part of aging”(n=4). 17 women indicated a most important reason; “other healthproblems more important”(n=4) and “normal part of aging”(n=3) were the most frequentlychosen. No one chose embarrassment as the most important reason. Conclusion: Consistentwith other reports, participants who had discussed FI in the past had more severe FI thanthose who had not. Some women who indicated FI in the past 4 weeks, did not considerthemselves to have the problem for unclear reasons. Higher prioritization of other healthproblems, perception that they are able to manage FI on their own, and belief that FI is anormal part of aging were the most common reasons for not discussing FI with clinicians.

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Effect of Extracorporeal Magnetic Stimulation of Sacral Nerve On AnorectalFunction in Patients with Fecal IncontinenceJoon Seong Lee, Eun Jung Kang, Hee Hyuk Im, Yun Jung, Su Jin Hong, Bong Min Ko,Jin Oh Kim, Joo Young Cho, Moon Sung Lee, Chan Sup Shim, Boo Sung Kim

Background: Sacral nerve electric-stimulation is a new therapeutic approach for patientswith fecal incontinence. The action mechanism of sacral nerve stimulation (SNS) to treat fecalincontinence remains poorly understood. Recent development of extracorporeal magneticstimulation reveals promising results in the treatment of fecal incontinence without invasiveelectrode placement. Aim: To evaluate anorectal physiologic effects of extracorporealmagneticstimulation (ECMS) of the sacral nerve in patients with fecal incontinence. Methods: Anorectalmanometry and rectal barostat studies were performed before and after magnetic stimulationof the sacral nerve (10 patients after first session, 9 patients after 8 sessions) in 12 patientswith fecal incontinence. ECMS of the sacral nerve was performed by arm-type magneticstimulator with the patient in the supine position. The intensity used for ECMS was 40-100% of maximal level, and stimulations of 10 Hz were repeated in 3 sec on, 3 sec offcycles for 15 minutes and stimulation of 50zHz were repeated in 3 sec on, 6 sec off cyclesfor 15 minutes in each patient. Results: After ECMS, there were no statically significantdifferences in various parameters including anal sphincter tone by anorectal manometry.Sensitivity index after 1 session of ECMS tended to decrease compared with basal level(39.5± 15.2%, and 22.5 ± 16.7%, p=0.057). Maximal tolerable volume after 8 session of ECMSwas significantly decreased (196.6± 80.6 ml to 152 ± 67.6 ml, p<0.009). Conclusion: Themechanism of ECMS of sacral nerve may relate to rectal sensitivity and decreased maximaltolerable volume through sacral nerve stimulation.

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Development of a Three-Dimensional Physiological Model of ColonicLongitudinal Smooth Muscle In Vitro Lined Up in Longitudinal AxisShreya Raghavan, Mai Lam, Lesley L. Foster, Robert R. Gilmont, Sita Somara, ShuichiTakayama, Khalil N. Bitar

Background: Crohn's Disease (CD) has high morbidity and mortality rates, incurring expens-ive healthcare costs and related complications leading to resections and Short Bowel Syn-drome. CD manifests itself as diarrhea and abdominal pain implicating abnormal colonicmotility that could be attributed to altered smoothmuscle function. Hypothesis: The objectiveof this study was to develop a physiologically functional three-dimensional (3-D) model ofthe colonic longitudinal smooth muscle cells, lined up along their longitudinal axis. Methods:Longitudinal smooth muscle cells isolated from rabbit sigmoid colon were grown to conflu-ency on regular tissue culture plastic. Cultured cells were seeded at high densities (500,000cells/35mm plate) on to laminin coated Sylgard surfaces with defined wavy micro-topo-graphies. While the laminin promoted cell adhesion, the wavy patterns allowed the longitud-inal cells to orient themselves along the same axis. Addition of fibrin to the aligned cellmonolayer surface resulted in delamination and the self-organization in 7-10 days, of thelongitudinal cells into a string (1.2 x 3.5 cm) anchored to pinned down laminin coated silksutures. Results: Examination of force generation in a 1cm long bioengineered string showedthe following: 1) 1 μM Acetylcholine (ACh) induced sustained rapid rising contractionresulting in the generation of 11.3 μN force, in the presence of Calcium, and a 1.6 foldlower force of 7 μN in the absence of extracellular calcium. 2) ACh induced contractionswere abolished in the presence of 1μM Calphostin-C, a PKC-α inhibitor, showing an averagedrop in baseline force by up to 10 μN. 3) ACh induced contractions showed a 2.5-folddecrease in force generation in the presence of 1 μM Vasoactive Intestinal Peptide (VIP) 4)1 μM Phorbol dibutyrate (PdBU) induced further contractions post treatment with ACh,both in the presence and absence of extracellular calcium. Summary: Bioengineered 3-Dlongitudinal smooth muscle presents the ability to generate force, and respond to contractileagonists and relaxant neurotransmitters. The bioengineered constructs also maintain theircalcium dependence characteristics. Conclusion: This is a novel physiologically relevant InVitro 3-D model of the colonic longitudinal smooth muscle layer that could be used toinvestigate the underlying pathophysiology in dysfunctional colonic motility associated withinflammation in CD, and serves also as possible implantable smooth muscle strips. Supportedby NIH/NIDDK 057020

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Assessment of Obstructive Defecation By High Resolution ManometryCompared to Magnetic Resonance DefecographyHeiko Fruehauf, Henriette Heinrich, Elad Kaufman, Oliver Goetze, Dominik Weishaupt,Michael Fried, Mark Fox

Background: Patients with obstructive defecation may have abnormalities of anorectal func-tion or structure. Standard investigation bymanometry shows only fair agreement with patientsymptoms and defecography. Agreement between investigations has been recommended fordefinitive diagnosis. Anorectal high resolution manometry (HRM) may improve diagnosticaccuracy by differentiating pressure effects caused by contraction vs. straining and by avoiding

A-220AGA Abstracts

artifacts caused by movement of the catheter relative to the sphincter during straining. Aims:This study compared the findings of HRM with magnetic resonance (MR) defecography inthe clinical assessment of patients presenting with obstructive defecation defined by RomeIII criteria as straining at stool with the sensation of incomplete evacuation, sensation ofblockage or digital facilitation. Methods: HRM was performed by a solid state catheter with10 circumferential sensors at 6mm separation across the anal canal and 2 placed 5cmproximal in the rectum (Manoscan AR 360, SSI, USA). Resting tone squeeze pressure anddynamic pressure activity during bearing down were analyzed. Findings were referred toMR defecography (1.5T, Philips, NL) performed after insertion of 250ml water based gellabeled with Gd-DOTA paramagnetic contrast as reference standard for pelvic floor anatomyand function. Results: 18 consecutive patients (17 female; age 23-90y) referredwith symptomsof obstructive defecation had full investigation. MRI diagnosis revealed anorectal dyssynergiawith paradoxical contraction in 5 and structural pathology in 12 patients (rectocele withintussuception (n=8), pelvic floor descent with enterocele (n=7) or prolapse (n=1) somecases had both rectocele and pelvic descent). Compared to patients with dyssynergia, thosewith structural pathology had lower mean resting pressures (59 vs. 94mmHg; p<0.03);however squeeze pressure rises were similar (110 vs. 138mmHg; n.s.). In functional dyssyner-gia on MRI, HRM showed paradoxical contraction or failure to increase abdominal pressurewithout anal relaxation (sensitivity 100% (5/5); specificity 92% (12/13)). One patient withnormal findings on MRI but paradoxical contraction on HRM had an anal fissure on examina-tion under anaesthesia. With structural pathology a pattern of high intra-rectal pressurewith a steep, positive pressure gradient was observed indicating obstruction in the analcanal. Conclusions: Diagnostic agreement between anorectal HRM and MR defecography ishigh and pressure measurements were able to accurately distinguish functional and structuralpathology as a cause of obstructive defecation.

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Factors Predicting Likelihood of Faecal Urgency After Radiotherapy forProstate CancerAdeel A. Bajwa, Paul Boulos, Anton V. Emmanuel

Introduction: Localised prostate cancer can be cured effectively with either surgery orradiotherapy (DXT), so predicting the likelihood of post DXT anorectal symptoms is keyto informing patients. We prospectively measured anorectal physiology (ARP) parametersin 25 patients receiving DXT for localised prostate cancer, aiming to identify pre-treatmentmeasures that predict the post-treatment symptom of faecal urgency.Methods: 26 consecutivepatients (mean age 67.8 years) receiving DXT with curative intent for localised prostatecancer were recruited. None had anorectal symptoms at baseline (Wexner score 0). Analmanometery, rectal distension thresholds, mucosal electrosensitivity, rectal mucosal bloodflow and rectal elastance (by barostat) were measured before and 4 months after treatmentcompletion. Results: 14/26 (54%) patients developed new symptoms of faecal urgency.Multiple regression analysis (with age and the above anorectal physiology measures asvariables) revealed pre treatment rectal elastance to be the only independent variable thatpredicted the development of post treatment faecal urgency (p=0.0334). Conclusions: Onlypre treatment rectal elastance was independently predictive of which patients develop thecommon post-DXT symptom of faecal urgency. We suggest that measuring rectal elastancecould be used to inform patients better of their potential risks of developing urgency post-DXT for localised prostate cancer.

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Immunoglobulins (IgGs) from Systemic Sclerosis (SSC) Patients Attenuate M3

Muscarinic Receptor Activation in Rat Internal Anal Sphincter (IAS) SmoothMuscle Cells (SMC)Jagmohan Singh, Vaibhav Mehendiratta, Francesco Del Galdo, Sergio A. Jimenez, SidneyCohen, Anthony J. DiMarino, Satish C. Rattan

Background: Systemic Sclerosis (SSc) is associated with severe gastrointestinal dysmotilityincluding rectoanal incontinence. It has been proposed that SSc IgGs affecting cholinergicneurotransmission via M3 muscarinic receptor (M3R) blockade may be responsible for thegastrointestinal pathophysiology. However, the effect of SSc IgGs on SMC function has notbeen studied. Methods: We determined the effect of SSc IgGs on M3R activation bybethanechol (methyl derivate of carbachol) (BeCh; 10-7 to 10-4 M) in SMC from rat IAS, beforeand after incubation with normal or SSc IgG. IgGs were purified from six GI symptomatic SScpatients and two normal volunteers, using protein G-sepharose columns. SMC lengths beforeand after incubation with IgGs were determined via computerized digital micrometry. Someexperiments were also performed in intact smooth muscle strips using digital chart recordingsystem to determine the effect of SSc and normal IgGs on BeCh-induced increase in theIAS tone. Results: In control experiments BeCh produced concentration-dependent SMCshortening. The control concentration-response curve (CRC) with BeCh was comparedfollowing incubation with different concentrations (0.3, 0.6 and 1 mg/ml) of IgGs from SScpatients and normal volunteers. IgGs from SSc patients caused significant and concentration-dependent inhibition of BeCh response (p < 0.05). IgGs from normal volunteers on theother hand, had no significant effect on BeCh response (p > 0.05). The maximal shorteningof 22.2 ± 1.2% caused by 10-4 M BeCh was significantly attenuated to 8.3 ± 1.2% by 1mg/ml of SSc IgGs (p < 0.05; n = 3). Similar concentration of normal IgG had no significanteffect (21.4 ± 1.4%; p > 0.05; n = 3). Experiments performed in smooth muscle stripsrevealed similar findings. BeCh-induced increase in the basal tone of the IAS was significantlyattenuated by SSc but not normal IgGs. SSc IgG-induced inhibition of BeCh response inthe smooth muscles was fully reversible. The SSc IgGs caused no significant effect (p >0.05) on K+ depolarization-induced CRC (5 mM to 40 mM KCl). Conclusion: SSc IgGsattenuate M3R activation in rat IAS SMC without affecting K+ depolarization-induced SMCcontraction. The attenuated smooth muscle response was reversible with antibody removal.The data suggest that SSc gastrointestinal dysmotility may be caused by autoantibodieswhich inhibit the function of M3R and may be reversible.