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1095 Gastroenterologist Care is Associated With Lower Mortality Risk in Hospitalized Ulcerative Colitis Patients
1096 Are Random Biopsies Still Useful for the Detection of Intraepithelial Neoplasia in IBD Patients Undergoing Surveillance Colonoscopy With Chromoendoscopy? Driffa Moussata, Matthieu Allez, Dominique Cazals-Hatem, Yoram Bouhnik, Philippe Bertheau, David Laharie, Jean-Marc Gornet, Anne Lavergne-Slove, Arnaud Bourreille, Hedia Brixi, Eric Fort, Jean-Marie Reimund, Carmen Stefanescu, Julien Branche, AnneLaure Pelletier, Philippe R. Marteau, Jacques Moreau, Marion Simon, Isabelle NionLarmurier, Franck Carbonnel, Jean-Francois Flejou, Françoise Berger, Bernard Flourie, Getaid Getaid BACKGROUND/AIM: Colonoscopy with panchromoendoscopy (CE) is superior to standard colonoscopy in detecting intraepithelial neoplasia (IEN) in patients with IBD. Whether there is still a need for random biopsies in unsuspicious mucosa after CE is controversial and recent guidelines recommend to perform random biopsies only if CE is not used. The aim of this study was to evaluate the performance of random biopsies in addition to the targeted biopsies of CE-visible lesions for the detection of IEN. METHODS: All patients with clinically quiescent IBD participating in an endoscopic program for detection of IEN using CE were prospectively included at 17 academic departments of Gastroenterology. All patients underwent complete colonoscopy according to a standardized procedure: on withdrawal, each 10 cm colonic segment was sprayed using 0.25% indigo carmine and all suspected lesions were classified according to Paris criteria and targeted biopsies or endoscopic resection were performed. In addition, 2 to 4 quadrantic random biopsies were then obtained every 10 cm from normal appearing mucosa according to standard guidelines. Histological slides with a suspicion of IEN were reviewed jointly by a panel of 5 expert GI pathologists in order to obtain a common diagnosis and to refrain from use of the indefinite dysplasia category. RESULTS: 900 colonoscopies were performed in 900 patients (478 F/422 M, mean age (± SD): 46 ± 14 yrs, mean disease duration: 17 ± 8 yrs). There were 369 (41 %) subjects with ulcerative colitis, 424 (47 %) with Crohn's colitis (involving at least 1/3 of colon) and 107 (12 %) with indeterminate colitis. Main results are reported in the Table.In 75 patients IEN/CRC was detected by only targeted biopsies from polypoid lesion or flat elevation, in 9 by only random biopsies and in 9 by both targeted and random biopsies. CONCLUSIONS: In this study, a special care was taken to follow classic and recent guidelines and to review biopsies by GI pathologists with extensive experience in the field of IEN. Although yield of additional systematic random biopsies is low, they allow to detect IEN, which were missed by targeted biopsies guided by chromoendoscopy, in 1 % of patients of this large series (900 patients). Follow up is however required to determine the impact of IEN found by random biopsies on care of IBD patients. Total number of biopsies and number of patients with IEN/ColoRectalCancer
1095 Gastroenterologist Care is Associated With Lower Mortality Risk in Hospitalized Ulcerative Colitis Patients Sanjay K. Murthy, A. Hillary Steinhart, Jill M. Tinmouth, Peter C. Austin, Geoffrey C. Nguyen Background and Aims: Health outcomes among hospitalized ulcerative colitis (UC) patients may be influenced by health care provider experience in UC management. We sought to assess the impact of in-hospital primary gastroenterologist care, relative to care provided by other specialists, on health outcomes in this population. Methods: A population-based cohort study was conducted of 4,278 UC patients hospitalized for a primary UC indication between 2002 and 2008 in Ontario, Canada. Health outcome rates between patients admitted to gastroenterologists and those admitted under other internists, general practitioners and general surgeons. The primary outcome was in-hospital mortality risk. Results: UC patients admitted under non-gastroenterologists had a higher in-hospital mortality rate (1.1 vs. 0.2 %, p<0.0001) but a similar in-hospital colectomy rate (5.4 vs. 4.9 %, p=0.69) as compared to UC patients admitted under gastroenterologists. After covariate adjustment, non-gastroenterologist care was associated with a higher in-hospital patient mortality risk than gastroenterologist care (adjusted odds ratio [aOR] 3.44, 95% confidence interval [CI] 1.10 - 10.81). Relative to gastroenterologist care, the higher mortality risk was restricted to patients admitted under other internists (OR 5.49, 95% CI 1.75 - 17.2) and general practitioners (OR 6.02, 95% CI 1.84 - 19.7); however, among non-colectomized patients, a higher mortality risk was also observed for those admitted under general surgeons (OR 5.21, 95% CI 1.38 19.8). Among patients discharged from hospital without undergoing colectomy, those who had been admitted under non-gastroenterologists had greater one-year risks of death (adjusted hazard ratio (aHR) 2.24, 95% CI 1.36 - 3.69) and non-elective hospital re-admission (aHR 1.14, 95% CI 1.02 - 1.28) as compared to patients who had been admitted under gastroenterologists. The one-year post-discharge mortality risk was similarly higher among patients admitted under other internists (aOR 1.92, 95% CI 1.06 - 3.47), general practitioners (aOR 2.18, 95% CI 1.29 - 3.69) and general surgeons (aOR, 2.34, 95% CI 1.22 - 2.54), relative to patients admitted under gastroenterologists. Hospital provider type did not impact colectomy risk in this cohort. Conclusions: Primary in-hospital gastroenterologist care may be associated with sustained mortality benefit for hospitalized UC patients. Optimized care strategies by experienced specialists may confer significant health advantages in this population.
1097 Once-Daily Versus Twice-Daily Mesalazine for Active Ulcerative Colitis: Efficacy Results From MOTUS, a Multicentre, Controlled, Randomised, Investigator-Blinded Study Bernard Flourie, Herve Hagege, Gilbert Tucat, Ad Masclee, Olivier Dewit, Chris Probert, Per Broberg, Aoucheta Djamila Background: In ulcerative colitis (UC), less frequent dosing of 5-ASA makes treatment easier and improves compliance. PODIUM demonstrated non-inferiority, and superiority (p=0.02), of 2 g once-daily (OD) vs 1g twice-daily (BD) Pentasa® sachet prolonged release granules for the maintenance of remission in UC (Dignass, CGH 2009). The objective of MOTUS (sponsor: Ferring Pharmaceuticals; NCT00737789) was to show non-inferiority of OD Pentasa® 4g sachet prolonged release granules (new concentrated formulation) vs standard 2g BD dosing for the induction of remission in active UC. Methods: Pts with active mildto-moderate UC were randomised to 5ASA granules 4g/d: 2x 2g OD or 1x 2g BD. All pts also received 5ASA enema (1g/d) for 4 wks. Primary endpoint: clinical and endoscopic remission at wk 8 (UC-DAI score ≤1). Secondary endpoints: clinical remission at wks 4, 8, 12 (normal stool frequency, no bloody stools, no active disease by physician's global assessment); mucosal healing at wk 8 (UC-DAI endoscopic mucosal appearance score ≤1). Statistical data are from intent-to-treat (ITT) and per-protocol (PP) analyses. Results: 206 pts enrolled (OD n=102; BD n=104). Primary endpoint met (Table): 5ASA 4g OD was noninferior to BD, the lower limit of the two-sided 95% CI of the difference in remission rate was -3%, within the pre-specified non-inferiority margin of -15%. Secondary endpoints for OD vs BD: clinical remission at wks 4, 8, 12: 39.8% vs 27.6% (p=0.07), 45.1% vs 40.8% (p=0.53), 92.4% vs 79.4% (p=0.13); mucosal healing at wk 8 by UC-DAI sub-score ≤1: 87.5% vs 71.1% (p=0.007). Conclusions: MOTUS showed non-inferiority of Pentasa® 4g OD vs BD in pts with active UC. The primary endpoint was met in all analysis groups. All secondary endpoints were also non-inferior for OD vs BD, with mucosal healing being significantly better with OD. The data are consistent with PODIUM (maintenance 5ASA). These studies show that OD treatment with 5ASA granules is at least as effective as BD dosing, allowing treatment to be personalised to pt preference.
Figure. In-hospital and one-year mortality rates among hospitalized UC patients based on most responsible physician provider in hospital. GI = gastroenterologist, IM = internal medicine specialist, GP = general practitioner, GS = general surgeon. P-values are for overall comparison between provider categories in bivariate analysis (a p-value based on chi-square test; b p-value based on log-rank test).
* Cochran-Mantel-Haenszel test for non-inferiority OD vs BD; NI = non-inferior
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AGA Abstracts
AGA Abstracts
a secreted as well as cell surface associated serine protease of Lp mediates selective degradation of IP-10 and other pro-inflammatory chemokines (e.g. Fractalkine) via direct proteolytic cleavage. Interestingly, tissue culture experiments revealed that conditioned media of Lp (CM Lp) selectively degrades tissue-distributed IP-10, suggesting tissue-accessibility of CM Lp. Moreover, intraperitoneal injection experiments in an experimental ileitis model revealed that CM Lp reduces intestinal IP-10 levels, lymphocyte recruitment and ileal inflammation. LC-MS/MS analysis of fractionated CM Lp indicated prtP-encoded lactocepin as active probiotic protease of Lp. This could be confirmed by immunoprecipitated active prtPencoded lactocepin, which degraded IP-10. Generation of a prtP-disruption mutant (lactocepin-negative) from a similarly active, but transformable, human Lactobacillus casei (Lc) isolate resulted in loss of its IP-10 degrading capacity, confirming probiotic prtP-encoded lactocepin as the active structure. Finally, feeding studies in T cell transferred Rag2-/- mice revealed, that the prtP-encoded lactocepin expressing Lc significantly reduces cecal IP-10 levels and cecal inflammation compared to the lactocepin-negative prtP-disruption mutant. Conclusion: We identified a probiotic prtP-encoded lactocepin as anti-inflammatory structure from a clinically relevant probiotic strain. This probiotic prtP-encoded lactocepin mediates antiinflammatory effects in tissue culture and mouse models of IBD via selective chemokine degradation.
1095 Gastroenterologist Care is Associated With Lower Mortality Risk in Hospitalized Ulcerative Colitis Patients Sanjay K. Murthy, A. Hillary Steinhart, Jill M. Tinmouth, Peter C. Austin, Geoffrey C. Nguyen Background and Aims: Health outcomes among hospitalized ulcerative colitis (UC) patients may be influenced by health care provider experience in UC management. We sought to assess the impact of in-hospital primary gastroenterologist care, relative to care provided by other specialists, on health outcomes in this population. Methods: A population-based cohort study was conducted of 4,278 UC patients hospitalized for a primary UC indication between 2002 and 2008 in Ontario, Canada. Health outcome rates between patients admitted to gastroenterologists and those admitted under other internists, general practitioners and general surgeons. The primary outcome was in-hospital mortality risk. Results: UC patients admitted under non-gastroenterologists had a higher in-hospital mortality rate (1.1 vs. 0.2 %, p<0.0001) but a similar in-hospital colectomy rate (5.4 vs. 4.9 %, p=0.69) as compared to UC patients admitted under gastroenterologists. After covariate adjustment, non-gastroenterologist care was associated with a higher in-hospital patient mortality risk than gastroenterologist care (adjusted odds ratio [aOR] 3.44, 95% confidence interval [CI] 1.10 - 10.81). Relative to gastroenterologist care, the higher mortality risk was restricted to patients admitted under other internists (OR 5.49, 95% CI 1.75 - 17.2) and general practitioners (OR 6.02, 95% CI 1.84 - 19.7); however, among non-colectomized patients, a higher mortality risk was also observed for those admitted under general surgeons (OR 5.21, 95% CI 1.38 19.8). Among patients discharged from hospital without undergoing colectomy, those who had been admitted under non-gastroenterologists had greater one-year risks of death (adjusted hazard ratio (aHR) 2.24, 95% CI 1.36 - 3.69) and non-elective hospital re-admission (aHR 1.14, 95% CI 1.02 - 1.28) as compared to patients who had been admitted under gastroenterologists. The one-year post-discharge mortality risk was similarly higher among patients admitted under other internists (aOR 1.92, 95% CI 1.06 - 3.47), general practitioners (aOR 2.18, 95% CI 1.29 - 3.69) and general surgeons (aOR, 2.34, 95% CI 1.22 - 2.54), relative to patients admitted under gastroenterologists. Hospital provider type did not impact colectomy risk in this cohort. Conclusions: Primary in-hospital gastroenterologist care may be associated with sustained mortality benefit for hospitalized UC patients. Optimized care strategies by experienced specialists may confer significant health advantages in this population.
1097 Once-Daily Versus Twice-Daily Mesalazine for Active Ulcerative Colitis: Efficacy Results From MOTUS, a Multicentre, Controlled, Randomised, Investigator-Blinded Study Bernard Flourie, Herve Hagege, Gilbert Tucat, Ad Masclee, Olivier Dewit, Chris Probert, Per Broberg, Aoucheta Djamila Background: In ulcerative colitis (UC), less frequent dosing of 5-ASA makes treatment easier and improves compliance. PODIUM demonstrated non-inferiority, and superiority (p=0.02), of 2 g once-daily (OD) vs 1g twice-daily (BD) Pentasa® sachet prolonged release granules for the maintenance of remission in UC (Dignass, CGH 2009). The objective of MOTUS (sponsor: Ferring Pharmaceuticals; NCT00737789) was to show non-inferiority of OD Pentasa® 4g sachet prolonged release granules (new concentrated formulation) vs standard 2g BD dosing for the induction of remission in active UC. Methods: Pts with active mildto-moderate UC were randomised to 5ASA granules 4g/d: 2x 2g OD or 1x 2g BD. All pts also received 5ASA enema (1g/d) for 4 wks. Primary endpoint: clinical and endoscopic remission at wk 8 (UC-DAI score ≤1). Secondary endpoints: clinical remission at wks 4, 8, 12 (normal stool frequency, no bloody stools, no active disease by physician's global assessment); mucosal healing at wk 8 (UC-DAI endoscopic mucosal appearance score ≤1). Statistical data are from intent-to-treat (ITT) and per-protocol (PP) analyses. Results: 206 pts enrolled (OD n=102; BD n=104). Primary endpoint met (Table): 5ASA 4g OD was noninferior to BD, the lower limit of the two-sided 95% CI of the difference in remission rate was -3%, within the pre-specified non-inferiority margin of -15%. Secondary endpoints for OD vs BD: clinical remission at wks 4, 8, 12: 39.8% vs 27.6% (p=0.07), 45.1% vs 40.8% (p=0.53), 92.4% vs 79.4% (p=0.13); mucosal healing at wk 8 by UC-DAI sub-score ≤1: 87.5% vs 71.1% (p=0.007). Conclusions: MOTUS showed non-inferiority of Pentasa® 4g OD vs BD in pts with active UC. The primary endpoint was met in all analysis groups. All secondary endpoints were also non-inferior for OD vs BD, with mucosal healing being significantly better with OD. The data are consistent with PODIUM (maintenance 5ASA). These studies show that OD treatment with 5ASA granules is at least as effective as BD dosing, allowing treatment to be personalised to pt preference.
Figure. In-hospital and one-year mortality rates among hospitalized UC patients based on most responsible physician provider in hospital. GI = gastroenterologist, IM = internal medicine specialist, GP = general practitioner, GS = general surgeon. P-values are for overall comparison between provider categories in bivariate analysis (a p-value based on chi-square test; b p-value based on log-rank test).
* Cochran-Mantel-Haenszel test for non-inferiority OD vs BD; NI = non-inferior
S-197
AGA Abstracts
AGA Abstracts
a secreted as well as cell surface associated serine protease of Lp mediates selective degradation of IP-10 and other pro-inflammatory chemokines (e.g. Fractalkine) via direct proteolytic cleavage. Interestingly, tissue culture experiments revealed that conditioned media of Lp (CM Lp) selectively degrades tissue-distributed IP-10, suggesting tissue-accessibility of CM Lp. Moreover, intraperitoneal injection experiments in an experimental ileitis model revealed that CM Lp reduces intestinal IP-10 levels, lymphocyte recruitment and ileal inflammation. LC-MS/MS analysis of fractionated CM Lp indicated prtP-encoded lactocepin as active probiotic protease of Lp. This could be confirmed by immunoprecipitated active prtPencoded lactocepin, which degraded IP-10. Generation of a prtP-disruption mutant (lactocepin-negative) from a similarly active, but transformable, human Lactobacillus casei (Lc) isolate resulted in loss of its IP-10 degrading capacity, confirming probiotic prtP-encoded lactocepin as the active structure. Finally, feeding studies in T cell transferred Rag2-/- mice revealed, that the prtP-encoded lactocepin expressing Lc significantly reduces cecal IP-10 levels and cecal inflammation compared to the lactocepin-negative prtP-disruption mutant. Conclusion: We identified a probiotic prtP-encoded lactocepin as anti-inflammatory structure from a clinically relevant probiotic strain. This probiotic prtP-encoded lactocepin mediates antiinflammatory effects in tissue culture and mouse models of IBD via selective chemokine degradation.