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Mo2026 Methane on Breath Test Predicts Altered Rectal Sensation During High Resolution Anorectal Manometry
compare to the non-methane groups (49.6±27.0 ml, p=0.04). However, there was no significant difference in rectal sensation among the non-methane groups. Rate of success for balloon expulsion test was similar among the groups. Conclusions: Presence of methane on lactulose breath test appears to be associated with a relative rectal hyposensitivity in response to stepwise rectal distention compared to all other subjects presenting for high resolution anorectal manometry. This phenomenon may be due to association of methane gas with chronic constipation. Mo2027 Effects of Vaginal Delivery on Anorectal Parameters and Rectal Sensation Measurements in a Fecal Incontinence Cohort Jason Baker, William D. Chey, Richard J. Saad, Stacy B. Menees Background: Vaginal delivery is recognized as a risk factor for fecal incontinence (FI). Reasons for FI following childbirth include sphincter tears and pelvic floor weakness. Limited data exists regarding anorectal physiology and parity. Aims: Assess for differences in anorectal muscle strength and rectal sensation between women with and without a history of vaginal delivery. Methods: We performed a retrospective analysis in females (≥18 years of age) referred for anorectal manometry (ARM) for FI at a single tertiary center from January 2002 to October 2013. Demographics (age, race, and body mass index {BMI}, ARM parameters, rectal sensation measurements, and number of vaginal deliveries) were collected. ARM parameters consisted of high pressure zone-HPZ (cm), resting anal sphincter pressure (mmHg), maximum anal sphincter pressure (mmHg); rectal sensation measurements comprised of first sensation to defecate (cc), urge to defecate (cc), and maximum tolerated (cc). Patients were stratified age-brackets (18-29, 30-39-, 40-54, 55-69, and ≥70) for a second analysis. Analysis consisted of ANOVA to determine differences between ARM parameters and number of vaginal deliveries. An independent t-test was calculated assessing differences between nulliparous and all vaginal deliveries. A multiple linear regression model was used to correct for age and BMI. Results: Data from 705 patients (Mean age of cohort 59.2, mean BMI 28.9, and 90% Caucasian) was analyzed. Vaginal delivery stratification is depicted in Table 1. There is a statistically significant difference in resting and maximum anal sphincter pressures between nulliparous vs. vaginal delivery groups (See Table 2). This finding was persistent after adjusting for age and BMI (p=0.000).There was no linear relationship between ARM parameters and rectal sensation measurements between increasing vaginal delivers compared to the nulliparous group. Stratified age-brackets elicited limited differences between nulliparous vs. number of experienced vaginal deliveries:40-54 HPZ following 3 vaginal deliveries (3.95 vs.3.38, p= 0.01), 55-69 resting anal sphincter pressure following 2 vaginal deliveries (51.94 vs. 43.94, p=0.05), maximum anal sphincter pressure following 1 vaginal delivery (95.33 vs. 72.75, p= 0.03), and first sensation to defecate following 5 or more vaginal deliveries (81.67 vs. 43.43, p=0.02). Conclusion: One or more vaginal deliveries do have an impact on resting and maximum anal sphincter pressures. However, there is no diminishing cumulative effect related to ARM parameters and rectal sensation measurements with increasing number of vaginal deliveries. Further investigation is needed to determine clinical relevance of our findings. Table 1: Number of Vaginal Deliveries for the FI Cohort
Mo2025 Patient Preference for Defining Success in Fecal Incontinence Treatment Trials Steve Heymen, Olafur S. Palsson, Sung M. Kim, Stefanie Twist, William E. Whitehead Background: Fecal incontinence (FI) affects 9% of non-institutionalized U.S. adults and may severely impact quality of life. In recent clinical trials evaluating new treatments for regulatory approval, the primary outcome is often the proportion of "responders", defined as anyone with at least a 50% reduction in FI frequency. However, some patients have objected that a 50% reduction is not enough to restore quality of life and would not be regarded by them as a "success". Aim: To identify patient preferences for the best way to identify what constitutes success in the treatment of FI. Methods: 23 individuals with FI participated in one of six 2-hour online moderated chatroom discussions in groups of 2-7 patients. Participation was anonymous - only arbitrarily assigned IDs were used to identify patients in the focus groups. Topics covered included patient preferences for the terminology used to refer to FI, what should be included in the definition of FI (reported separately), and patient views on how to define a successful outcome of treatment. Participants were recruited via online advertisements, mass e-mails to the students and staff of the university, and our Center's research participant registry. Volunteers first logged onto a website where they gave informed consent to the research and answered standardized questionnaires on FI severity (Fecal Incontinence Severity Index, Constipation and Incontinence Questionnaire) and quality of life impact (Fecal Incontinence Quality of Life scale). They also signed up for one of several scheduled chatroom sessions. The sessions were moderated by the study investigators who combined open-ended questions (e.g., "How would you define success in a clinical trial?") with questions about whether specific responder definitions (e.g., "at least a 50% reduction") were acceptable to them. Results: There were 23 participants, 22 were females. Only 41% of subjects felt that a 50% reduction in FI symptoms reflected a meaningful treatment success. When asked how much reduction would be necessary to regard the treatment as successful, the average was a 75% reduction. Only 4 out of 23 subjects reported that a "cure" (100% reduction in FI frequency) was necessary to count a treatment as successful. Adequate relief" was endorsed by 52% of subjects as a good way to measure results, although several commented that they did not know what "adequate relief" means. Conclusions: The primary outcome that has been accepted by regulatory agencies for approval of new treatments - 50% reduction in treatment - is not considered to be sufficient for treatment to be successful by the majority of patients, but neither would they require a complete cure. On average, these FI patients felt that a 75% reduction in frequency would be required for a successful treatment outcome. [Supported by Salix Pharmaceuticals and AHRQ grant R01 HS018695]
Table 2: ARM Parameters and Rectal Sensation differences between Nulliparous women and All Vaginal Deliveries.
Mo2026 Methane on Breath Test Predicts Altered Rectal Sensation During High Resolution Anorectal Manometry Ali Rezaie, Kathleen Shari Chua, Christopher Chang, Thomas Kemmerly, Mark Pimentel A large scale published meta-analysis has suggested an association between methane on lactulose breath test and chronic constipation. In animal studies, methane appears to slow intestinal transit and produce abnormal motor responses. However, no study has examined the anorectal sensory responses in subjects producing methane gas. Using two large scale databases, we evaluated subjects who had both an anorectal manometry and lactulose breath test. Methods: Records of all patients who underwent high resolution anorectal manometry (HRARM) from Oct 2007 to Apr 2013 were extracted. Using date of birth, first and last name a deterministic record linkage was performed with a separate database of breath test studies. Breath tests were classified into four categories: Normal, positive hydrogen, positive methane (≥3 ppm) and flat line (i.e. no variation in hydrogen levels through 90 minutes of testing). In addition to balloon expulsion test, HRARM findings including resting and squeeze anal sphincter pressures, along with sensation of fullness and urge to defecate with stepwise graded rectal balloon distensions were compared among breath test categories. Results: HRARM database which houses 1,201 manometries was linked to our breath test database of 16,703 studies. A total of 519 breath tests corresponding to 365 subjects were identified. Of 365 subjects, 110 had normal breath test, 122 were hydrogen positive, 81 were methane positive and 52 were flat line. Among the four groups, no differences were seen in the resting and squeeze anal sphincter pressures. Methane positive subjects had a significantly elevated threshold for sensing defecation urge at 109.2±45.6 mL compared to 93.0±45.0 mL for negative breath tests, 87.1±42.4 mL for positive hydrogen breath test and 95.5±4.8 mL for flat line(p=0.02). When pooled together non-methane groups had a significantly lower volume threshold for defecation urge (89.8±43.6 ml) to methane producing subjects (109.2±45.6 ml, p=0.004). This was true even after controlling for baseline presenting diagnosis. Volume threshold for sensation of fullness showed and expected lognormal distribution and was higher in the methane positive subjects (54.3±25.1) as
Mo2028 The Anti-Nociceptive Effect of A-317491, a Selective P2X3 Receptor Antagonist, on Visceromotor Responses in a Rat Model for Post-Inflammatory Visceral Hypersensitivity Annemie Deiteren, Anouk de Wit, Laura van der Linden, Joris G. De Man, Tom G. Moreels, Paul A. Pelckmans, Benedicte Y. De Winter Background: P2X3 receptors (P2X3Rs) are believed to contribute to visceral hypersensitivity. To date, most experiments have been conducted in P2X3 knock-out mice or using nonselective P2X receptor antagonists in animal models of acute inflammatory visceral hypersensitivity. Besides, only limited data are available on the role of P2X3Rs in post-inflammatory hypersensitivity. Hence, the aim of our study was to investigate the effect of the selective P2X3R antagonist A-317491 in a rat model for post-inflammatory visceral hypersensitivity. Methods: Colitis was induced in Sprague-Dawley rats by a trinitrobenzenesulphonic acid enema (TNBS, 15 mg in 50% ethanol). The extent of colitis was confirmed by colonoscopy on day 3. From day 10 onwards, convalescence was monitored by repeated colonoscopy
S-721
AGA Abstracts
AGA Abstracts
7 on the 0-10 scale. Scores for all other terms ranged from 1-10. [Supported by Salix Pharmaceuticals and AHRQ grant R01 HS018695]
Mo2025 Patient Preference for Defining Success in Fecal Incontinence Treatment Trials Steve Heymen, Olafur S. Palsson, Sung M. Kim, Stefanie Twist, William E. Whitehead Background: Fecal incontinence (FI) affects 9% of non-institutionalized U.S. adults and may severely impact quality of life. In recent clinical trials evaluating new treatments for regulatory approval, the primary outcome is often the proportion of "responders", defined as anyone with at least a 50% reduction in FI frequency. However, some patients have objected that a 50% reduction is not enough to restore quality of life and would not be regarded by them as a "success". Aim: To identify patient preferences for the best way to identify what constitutes success in the treatment of FI. Methods: 23 individuals with FI participated in one of six 2-hour online moderated chatroom discussions in groups of 2-7 patients. Participation was anonymous - only arbitrarily assigned IDs were used to identify patients in the focus groups. Topics covered included patient preferences for the terminology used to refer to FI, what should be included in the definition of FI (reported separately), and patient views on how to define a successful outcome of treatment. Participants were recruited via online advertisements, mass e-mails to the students and staff of the university, and our Center's research participant registry. Volunteers first logged onto a website where they gave informed consent to the research and answered standardized questionnaires on FI severity (Fecal Incontinence Severity Index, Constipation and Incontinence Questionnaire) and quality of life impact (Fecal Incontinence Quality of Life scale). They also signed up for one of several scheduled chatroom sessions. The sessions were moderated by the study investigators who combined open-ended questions (e.g., "How would you define success in a clinical trial?") with questions about whether specific responder definitions (e.g., "at least a 50% reduction") were acceptable to them. Results: There were 23 participants, 22 were females. Only 41% of subjects felt that a 50% reduction in FI symptoms reflected a meaningful treatment success. When asked how much reduction would be necessary to regard the treatment as successful, the average was a 75% reduction. Only 4 out of 23 subjects reported that a "cure" (100% reduction in FI frequency) was necessary to count a treatment as successful. Adequate relief" was endorsed by 52% of subjects as a good way to measure results, although several commented that they did not know what "adequate relief" means. Conclusions: The primary outcome that has been accepted by regulatory agencies for approval of new treatments - 50% reduction in treatment - is not considered to be sufficient for treatment to be successful by the majority of patients, but neither would they require a complete cure. On average, these FI patients felt that a 75% reduction in frequency would be required for a successful treatment outcome. [Supported by Salix Pharmaceuticals and AHRQ grant R01 HS018695]
Table 2: ARM Parameters and Rectal Sensation differences between Nulliparous women and All Vaginal Deliveries.
Mo2026 Methane on Breath Test Predicts Altered Rectal Sensation During High Resolution Anorectal Manometry Ali Rezaie, Kathleen Shari Chua, Christopher Chang, Thomas Kemmerly, Mark Pimentel A large scale published meta-analysis has suggested an association between methane on lactulose breath test and chronic constipation. In animal studies, methane appears to slow intestinal transit and produce abnormal motor responses. However, no study has examined the anorectal sensory responses in subjects producing methane gas. Using two large scale databases, we evaluated subjects who had both an anorectal manometry and lactulose breath test. Methods: Records of all patients who underwent high resolution anorectal manometry (HRARM) from Oct 2007 to Apr 2013 were extracted. Using date of birth, first and last name a deterministic record linkage was performed with a separate database of breath test studies. Breath tests were classified into four categories: Normal, positive hydrogen, positive methane (≥3 ppm) and flat line (i.e. no variation in hydrogen levels through 90 minutes of testing). In addition to balloon expulsion test, HRARM findings including resting and squeeze anal sphincter pressures, along with sensation of fullness and urge to defecate with stepwise graded rectal balloon distensions were compared among breath test categories. Results: HRARM database which houses 1,201 manometries was linked to our breath test database of 16,703 studies. A total of 519 breath tests corresponding to 365 subjects were identified. Of 365 subjects, 110 had normal breath test, 122 were hydrogen positive, 81 were methane positive and 52 were flat line. Among the four groups, no differences were seen in the resting and squeeze anal sphincter pressures. Methane positive subjects had a significantly elevated threshold for sensing defecation urge at 109.2±45.6 mL compared to 93.0±45.0 mL for negative breath tests, 87.1±42.4 mL for positive hydrogen breath test and 95.5±4.8 mL for flat line(p=0.02). When pooled together non-methane groups had a significantly lower volume threshold for defecation urge (89.8±43.6 ml) to methane producing subjects (109.2±45.6 ml, p=0.004). This was true even after controlling for baseline presenting diagnosis. Volume threshold for sensation of fullness showed and expected lognormal distribution and was higher in the methane positive subjects (54.3±25.1) as
Mo2028 The Anti-Nociceptive Effect of A-317491, a Selective P2X3 Receptor Antagonist, on Visceromotor Responses in a Rat Model for Post-Inflammatory Visceral Hypersensitivity Annemie Deiteren, Anouk de Wit, Laura van der Linden, Joris G. De Man, Tom G. Moreels, Paul A. Pelckmans, Benedicte Y. De Winter Background: P2X3 receptors (P2X3Rs) are believed to contribute to visceral hypersensitivity. To date, most experiments have been conducted in P2X3 knock-out mice or using nonselective P2X receptor antagonists in animal models of acute inflammatory visceral hypersensitivity. Besides, only limited data are available on the role of P2X3Rs in post-inflammatory hypersensitivity. Hence, the aim of our study was to investigate the effect of the selective P2X3R antagonist A-317491 in a rat model for post-inflammatory visceral hypersensitivity. Methods: Colitis was induced in Sprague-Dawley rats by a trinitrobenzenesulphonic acid enema (TNBS, 15 mg in 50% ethanol). The extent of colitis was confirmed by colonoscopy on day 3. From day 10 onwards, convalescence was monitored by repeated colonoscopy
S-721
AGA Abstracts
AGA Abstracts
7 on the 0-10 scale. Scores for all other terms ranged from 1-10. [Supported by Salix Pharmaceuticals and AHRQ grant R01 HS018695]