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AGA Abstracts [HB] and UC disease activity index [UCDAI] and Short Inflammatory Bowel Disease Question- naire score [SIBDQ]) scores porspectively tabulated at time of routine clinic visits. Three groups of pts (141 in each group) > 65 yrs, 64- 41 yrs, and < 40 yrs were included in the analysis and all pts with 5 or more scores comprised the study population. Influence of disease type (fistulizing, penetrating, inflammatory, and stricturing), disease duration, and extent of involvement as well as co-morbidities such as cardiovascular (CV)/pulmonary diseases, diabetes mellitus (DM) type I/II, and psychological disorders were also noted as potential confounding factors. Analysis was performed using a general linear model. Results: In all, fistulizing IBD phenotype, extent of disease, HB score, and psychological disorder had the most significant effect on SIBDQ with P values of 0.0166, 0.0278, <0.0001, and 0.0003, respectively. Age, disease duration, CV disease, and pulmonary disease did not affect SIBDQ significantly (P = 0.9080, 0.5004, and 0.0661, respectively). Conclusion: HRQoL in IBD patients is negatively influenced by the fistulizing IBD phenotype, extent of disease, disease severity and presence of psychological disorders. Advanced age at diagnosis is not a predictor of poor HRQoL. Tu1313 Radiation-Induced Anorectal Dysfunction Remains Persistent Whilst Rectal Bleeding Stabilises After Radiation Therapy (RT) for Prostate Carcinoma (CAP) Rochelle J. Botten, Julie Butters, Addolorata C. DiMatteo, Richard H. Holloway, Robert J. Fraser, Eric Yeoh Chronic radiation proctitis (CRP), characterised by persistence of symptoms of increased frequency and urgency of defaecation and rectal bleeding ≥ 3 months after RT for CaP, is an under-estimated cause of morbidity 1 together with poorly documented pathophysiology, natural history and often unsatisfactory treatment 2 . Patients are frequently unaware of the potential long-term sequelae despite technological advances in RT 3 . The aims of this study were to determine the pathophysiology and natural history of symptoms related to CRP. Methods: 34 patients with localised CaP (median age 68(54-79 years)) were randomised to receive either 64Gy/32fractions/6.5weeks (n =19) or 55 Gy/20fractions/4weeks (n =15) RT dose schedule (using a 2D and later a 3D technique in 21 and 13 patients, respectively). Each patient was evaluated before RT and at one month and annually for 5 years after completion for: (i) GI symptoms (Modified LENT-SOMA questionnaire including effect on activities of daily living), (ii) anorectal motor and sensory function (manometry and graded balloon distension) and (iii) anal sphincter morphology (endoanal ultrasound). Data were analysed by repeated measures ANOVA for changes with time and by 2 way ANOVA for differences according to RT schedule and technique. p<0.05 was considered significant in all analyses. Results: Total LENT-SOMA GI symptom scores (median, range) increased after RT and remained above baseline levels up to 5 years after RT (table). Activities of daily living were impaired in 48% of the patients, with 44% reporting urgency of defecation and 21% troublesome rectal bleeding 5 years after completing RT. Increased GI symptoms were associated with reductions in both basal anal sphincter pressures and responses to squeeze and increased intra-abdominal pressure as well as rectal compliance. There was an increased perception of rectal distension. Anal sphincter morphology was unchanged. GI symptom scores, parameters of anorectal function and anal sphincter morphology were unaffected by differing RT dose schedules and techniques. Conclusions: Increased total GI symptoms 5 years after RT impact on the daily activities of approximately half of the patients and are associated with evidence of anorectal dysfunction independent of RT dose schedule and RT technique. Patients undergoing RT for CaP should be provided with information regarding delayed symptoms. 1 Yeoh et al, Am J Gastro 99:361-369, 2004, 2 Yeoh, Curr Opin Supp Palliat Care, 2:40-44, 2008, 3 Smeenk et al Radiother Oncol 95:277-282, 2010 S-794 AGA Abstracts *p<0.05 cf baseline, **p<0.01 cf baseline, ***p<0.001 cf baseline Tu1314 Overt Rectal Prolapse: Is Incontinence Really Improved After the Laparoscopic Rectopexy? Laurent Siproudhis, Laurent Siproudhis, Guillaume Bouguen, Caroline Couffon, Isabelle Berkelmans, Veronique Desfourneaux, Jean-François Bretagne Continence disorders are thought to improve after rectopexy for overt rectal prolapse (RP), but the level of improvement is usually not specified. The aim of this study was to quantify incontinence before and after laparoscopic rectopexy in patients suffering from RP. Patients and methods: 94 patients (mean age 55±16 years, 87 women) underwent laparoscopic rectopexy to treat a RP between 2003 and 2009. Symptomatic and functional data were collected before and after surgery (mean follow 37±26 months) by self-administered question- naires. The analysis focused on functional disorders before and after surgery: Cleveland (fecal incontinence), Kess (constipation), GIQLI (quality of life), UID and KBO (urinary urgency and incontinence). Incontinence was considered when the Cleveland score remained > 5 after surgery. Results: 87% rated good to excellent results and 95% would accept a new surgery in the same conditions. There was an improvement in continence in 62 (66%) and symptom score decreased significantly (-3.2±6.1, p = 0.001). After surgery, continence score remained however positive in 83 and it was > 5 for 52 (55%); 52 (55%) reported urge incontinence and 31 (33%) had a passive leakage. Incontinence for liquid, solid stool and protection afflicted respectively 49 (52%), 36 (38%) and 50 (53%) patients. No physiological data (manometry) or anatomic (defecography, anal ultrasonography) was associated with some level of improvement. In contrast, patient age (59.7±15.4 vs. 49.3±16.4 years, p = 0.002), symptom duration before surgery (63.1±76 vs. 30.7±32.8 months, p = 0.027), pre- operative urinary incontinence score (11.1±10.8 vs. 4.5±6.4, p = 0.002) and fecal incontin- ence score (12.3±5.3 vs. 7.7±6.1, p <0.001) were significantly higher in patients suffering from post-operative incontinence. Conclusion: Despite some decrease of incontinence in two third of patients who underwent surgery for PR, the level of improvement remains somewhat low for more than half of them. Therefore, it is mandatory to quantify residual functional disorders for a best management after surgery Tu1315 Proteinase-Activated Receptor-1 (PAR1) and PAR2 but Not PAR4 Mediate Relaxation of Guinea-Pig Internal Anal Sphincter Shih-Che Huang Proteinase-activated receptor-1 (PAR1), PAR2 and PAR4 mediate contraction in the colon. Effects mediated by PARs in the internal anal sphincter were not known. The aim of this study was to investigate effects mediated by PAR1, PAR2 and PAR4 in the internal anal sphincter In Vitro. We measured relaxation of transverse strips from the guinea-pig internal anal sphincter caused by PAR1, PAR2 and PAR4 agonists using isometric transducers. PAR1 agonists, thrombin, TFLLR-NH2 and SFLLRN-NH2, as well as PAR2 agonists, including trypsin, 2-furoyl-LIGRLO-NH2, SLIGRL-NH2 and SLIGKV-NH2, caused moderate, dose- dependent relaxation of the internal anal sphincter. In contrast, FSLLR-NH2, a PAR1 control peptide, and VKGILS-NH2, a PAR2 control peptide, did not cause contraction or relaxation. These indicate the existence of PAR1 and PAR2 mediating relaxation of the internal anal sphincter. All three PAR4 agonists, including GYPGKF-NH2, GYPGQV-NH2 and AYPGKF- NH2, did not cause any relaxation or contraction, suggesting that PAR4 is not involved in internal anal sphincter motility. Furthermore, the relaxations caused by trypsin and 2-furoyl- LIGRLO-NH2 were not altered by atropine or tetrodotoxin, indicating that the PAR2 response was not neutrally mediated. In contrast, the relaxant responses of thrombin and TFLLR- NH2 were inhibited by atropine and tetrodotoxin, suggesting a neural effect. These results demonstrate that PAR1 and PAR2 but not PAR4 mediate relaxation of the internal anal sphincter. Thrombin and trypsin relax the internal anal sphincter In Vitro.
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s[HB] and UCdisease activity index [UCDAI] and Short Inflammatory Bowel Disease Question-naire score [SIBDQ]) scores porspectively tabulated at time of routine clinic visits. Threegroups of pts (141 in each group) > 65 yrs, 64- 41 yrs, and < 40 yrs were included in theanalysis and all pts with 5 or more scores comprised the study population. Influence ofdisease type (fistulizing, penetrating, inflammatory, and stricturing), disease duration, andextent of involvement as well as co-morbidities such as cardiovascular (CV)/pulmonarydiseases, diabetes mellitus (DM) type I/II, and psychological disorders were also noted aspotential confounding factors. Analysis was performed using a general linear model. Results:In all, fistulizing IBD phenotype, extent of disease, HB score, and psychological disorderhad the most significant effect on SIBDQ with P values of 0.0166, 0.0278, <0.0001, and0.0003, respectively. Age, disease duration, CV disease, and pulmonary disease did notaffect SIBDQ significantly (P = 0.9080, 0.5004, and 0.0661, respectively). Conclusion:HRQoL in IBD patients is negatively influenced by the fistulizing IBD phenotype, extent ofdisease, disease severity and presence of psychological disorders. Advanced age at diagnosisis not a predictor of poor HRQoL.
Tu1313
Radiation-Induced Anorectal Dysfunction Remains Persistent Whilst RectalBleeding Stabilises After Radiation Therapy (RT) for Prostate Carcinoma(CAP)Rochelle J. Botten, Julie Butters, Addolorata C. DiMatteo, Richard H. Holloway, Robert J.Fraser, Eric Yeoh
Chronic radiation proctitis (CRP), characterised by persistence of symptoms of increasedfrequency and urgency of defaecation and rectal bleeding ≥ 3 months after RT for CaP, isan under-estimated cause of morbidity1 together with poorly documented pathophysiology,natural history and often unsatisfactory treatment2. Patients are frequently unaware of thepotential long-term sequelae despite technological advances in RT3. The aims of this studywere to determine the pathophysiology and natural history of symptoms related to CRP.Methods: 34 patients with localised CaP (median age 68(54-79 years)) were randomisedto receive either 64Gy/32fractions/6.5weeks (n =19) or 55 Gy/20fractions/4weeks (n =15)RT dose schedule (using a 2D and later a 3D technique in 21 and 13 patients, respectively).Each patient was evaluated before RT and at one month and annually for 5 years aftercompletion for: (i) GI symptoms (Modified LENT-SOMA questionnaire including effect onactivities of daily living), (ii) anorectal motor and sensory function (manometry and gradedballoon distension) and (iii) anal sphincter morphology (endoanal ultrasound). Data wereanalysed by repeated measures ANOVA for changes with time and by 2 way ANOVA fordifferences according to RT schedule and technique. p<0.05 was considered significant inall analyses. Results: Total LENT-SOMA GI symptom scores (median, range) increased afterRT and remained above baseline levels up to 5 years after RT (table). Activities of dailyliving were impaired in 48% of the patients, with 44% reporting urgency of defecation and21% troublesome rectal bleeding 5 years after completing RT. Increased GI symptoms wereassociated with reductions in both basal anal sphincter pressures and responses to squeezeand increased intra-abdominal pressure as well as rectal compliance. There was an increasedperception of rectal distension. Anal sphincter morphology was unchanged. GI symptomscores, parameters of anorectal function and anal sphincter morphology were unaffected bydiffering RT dose schedules and techniques. Conclusions: Increased total GI symptoms 5years after RT impact on the daily activities of approximately half of the patients and areassociated with evidence of anorectal dysfunction independent of RT dose schedule and RTtechnique. Patients undergoing RT for CaP should be provided with information regardingdelayed symptoms. 1 Yeoh et al, Am J Gastro 99:361-369, 2004, 2 Yeoh, Curr Opin Supp PalliatCare, 2:40-44, 2008, 3 Smeenk et al Radiother Oncol 95:277-282, 2010
S-794AGA Abstracts
*p<0.05 cf baseline, **p<0.01 cf baseline, ***p<0.001 cf baseline
Tu1314
Overt Rectal Prolapse: Is Incontinence Really Improved After the LaparoscopicRectopexy?Laurent Siproudhis, Laurent Siproudhis, Guillaume Bouguen, Caroline Couffon, IsabelleBerkelmans, Veronique Desfourneaux, Jean-François Bretagne
Continence disorders are thought to improve after rectopexy for overt rectal prolapse (RP),but the level of improvement is usually not specified. The aim of this study was to quantifyincontinence before and after laparoscopic rectopexy in patients suffering from RP. Patientsand methods: 94 patients (mean age 55±16 years, 87 women) underwent laparoscopicrectopexy to treat a RP between 2003 and 2009. Symptomatic and functional data werecollected before and after surgery (mean follow 37±26months) by self-administered question-naires. The analysis focused on functional disorders before and after surgery: Cleveland(fecal incontinence), Kess (constipation), GIQLI (quality of life), UID and KBO (urinaryurgency and incontinence). Incontinence was considered when the Cleveland score remained> 5 after surgery. Results: 87% rated good to excellent results and 95% would accept a newsurgery in the same conditions. There was an improvement in continence in 62 (66%) andsymptom score decreased significantly (-3.2±6.1, p = 0.001). After surgery, continence scoreremained however positive in 83 and it was > 5 for 52 (55%); 52 (55%) reported urgeincontinence and 31 (33%) had a passive leakage. Incontinence for liquid, solid stool andprotection afflicted respectively 49 (52%), 36 (38%) and 50 (53%) patients. No physiologicaldata (manometry) or anatomic (defecography, anal ultrasonography) was associated withsome level of improvement. In contrast, patient age (59.7±15.4 vs. 49.3±16.4 years, p =0.002), symptom duration before surgery (63.1±76 vs. 30.7±32.8 months, p = 0.027), pre-operative urinary incontinence score (11.1±10.8 vs. 4.5±6.4, p = 0.002) and fecal incontin-ence score (12.3±5.3 vs. 7.7±6.1, p <0.001) were significantly higher in patients sufferingfrom post-operative incontinence. Conclusion: Despite some decrease of incontinence intwo third of patients who underwent surgery for PR, the level of improvement remainssomewhat low for more than half of them. Therefore, it is mandatory to quantify residualfunctional disorders for a best management after surgery
Tu1315
Proteinase-Activated Receptor-1 (PAR1) and PAR2 but Not PAR4 MediateRelaxation of Guinea-Pig Internal Anal SphincterShih-Che Huang
Proteinase-activated receptor-1 (PAR1), PAR2 and PAR4 mediate contraction in the colon.Effects mediated by PARs in the internal anal sphincter were not known. The aim of thisstudy was to investigate effects mediated by PAR1, PAR2 and PAR4 in the internal analsphincter In Vitro. We measured relaxation of transverse strips from the guinea-pig internalanal sphincter caused by PAR1, PAR2 and PAR4 agonists using isometric transducers. PAR1agonists, thrombin, TFLLR-NH2 and SFLLRN-NH2, as well as PAR2 agonists, includingtrypsin, 2-furoyl-LIGRLO-NH2, SLIGRL-NH2 and SLIGKV-NH2, caused moderate, dose-dependent relaxation of the internal anal sphincter. In contrast, FSLLR-NH2, a PAR1 controlpeptide, and VKGILS-NH2, a PAR2 control peptide, did not cause contraction or relaxation.These indicate the existence of PAR1 and PAR2 mediating relaxation of the internal analsphincter. All three PAR4 agonists, including GYPGKF-NH2, GYPGQV-NH2 and AYPGKF-NH2, did not cause any relaxation or contraction, suggesting that PAR4 is not involved ininternal anal sphincter motility. Furthermore, the relaxations caused by trypsin and 2-furoyl-LIGRLO-NH2 were not altered by atropine or tetrodotoxin, indicating that the PAR2 responsewas not neutrally mediated. In contrast, the relaxant responses of thrombin and TFLLR-NH2 were inhibited by atropine and tetrodotoxin, suggesting a neural effect. These resultsdemonstrate that PAR1 and PAR2 but not PAR4 mediate relaxation of the internal analsphincter. Thrombin and trypsin relax the internal anal sphincter In Vitro.
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