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Ano-rectal function and histological changes after ileo neo-rectal anastomosis, an alternative procedure to the ileo-Anal pouch
April 2000
Conclusions: These findings suggest that protective effect caused by ES enemas would be mediated by endogenous PGs via COX-I. Thus, ESS enemas may be a good candidate for clinical application because of its preventive effect on acute aggravation of colitis in IBD patients.
3030 ANO·RECTAL FUNCTION AND HISTOLOGICAL CHANGES AF· TER ILEO NEO·RECTAL ANASTOMOSIS, AN ALTERNATIVE PROCEDURE TO THE ILEO·ANAL POUCH. Gunnar I. Andriesse, Marguerite E. Schipper, Louis M. Akkermans, Hein G. Gooszen, Theo 1. Vroonhoven, Cees 1. Laarhoven, Univ Med Ctr, Utrecht, Netherlands. The Ileo Neo-Rectal Anastomosis (lNRA) is an alternative restorative procedure for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) and has been developed in order to reduce the high pouch-related complication (15-35%) and failure rate (6.5%) of the Ileo Pouch-Anal Anastomosis (IPAA). In contrast to IPAA the ano-rectum is preserved and the rectal mucosa is excised and replaced by healthy, vascularised, ileal mucosa. The ultimate purpose, establishment of a compliant neo-rectal reservoir with a concordant low defecation frequency and full continence in the long-term is being addressed in this presentation. In 12 patients (10 UC + 2 FAP) an INRA was performed after subtotal colectomy, with a temporary diverting ileostomy for three months. Anorectal function was tested preoperatively and up to a median of 16 months postoperatively (range 12-22 months). The first sensation, urge sensation, capacity, compliance and anorectal electrosensibility were measured. Anal and rectal ultrasound were carried out to assess the transmural architecture of the neo-rectum. Furthermore histological aspects of neo-rectal mucosa ingrowth and maturation were assessed. The INRA procedure was successfully performed in all patients. Ano-rectal function tests revealed no change in anal sphincter resting (median 8 (6-13) kPa) and squeeze pressure (median 18 (7-35) kPa). Rectal capacity temorarily decreased considerably after INRA, but increased up to normal levels in 12 months (median 108 (56-300) vs 157 (130-225) ml, respectively). This is in accordance with increasing compliance of the neorectum and decreasing stoolfrequency. Anal electrosensibility was unchanged after INRA (median 7 (4-14) rnA), but rectal electrosensibility decreased from median 26 rnA (16-75) to 46 rnA (13-99). Ultrasound showed no structural damage to the anal sphincter and an anatomically normal intestinal wall. Histology showed villus atrophy and a mixed active and chronic inflammatory infiltrate at 6 weeks with recovery in time. At 6 months the villus architecture was restored with an intact goblet cell population and brush border and dissapearance of the inflammatory infiltrate. Although during the INRA procedure the anorectum is manipulated to great extend, anorectal function is perserved. Anorectal function, as well as the functional result after INRA are comparable to IPAA. Ileal mucosa transplantation is feasible with development of healthy neorectal mucosa.
3031 HERBAL THERAPIES USED BY PATIENTS FOR INFLAMMATORY BOWEL DISEASE ARE ANTIOXIDANT IN VITRO. Louise Langmead, Nadine Banna, Suat Loo, David S. Rampton, St Bartholomew's and The Royal London Sch of Medicine, London, United Kingdom. Background: Herbal remedies used by patients for the treatment of inflammatory bowel disease (mD) include Aloe vera gel (AV), the mucilaginous pulp of the leaves of the Aloe Barbadensis Miller plant, fenugreek (FG), an Ayurvedic therapy, slippery elm (SE) made from the bark of the slippery elm tree, and mixtures of herbs prescribed as Traditional Chinese Medicine (TCM). Each is claimed to soothe inflamed intestine. Reactive oxygen metabolites (ROM) are produced by inflamed colonic mucosa and may be pathogenic in IBO. Aminosalicylates are antioxidant and other such agents may have a therapeutic role in IBD. Aim: To assess the antioxidant effects of herbal remedies in a cell-free oxidant-generating system and in inflamed human colorectal biopsies. Methods: Luminol-enhanced chemiluminescence (CL) was used to detect ROM production by xanthine/xanthine oxidase, and from mucosal biopsies from patients with active ulcerative colitis incubated for 40 minutes in the presence of AV, FG, SE, TCM or inert vehicle. Results: In the cell-free system serial dilutions of AV (IC50= 1 in 100), SE (1 in 5000) and TCM (1 in 10000), but not FG, showed dose-dependent ROM scavenging effects. ROM release from inflamed mucosal biopsies was reduced after incubation with AV diluted 1 in 50 (17 (8-18) cps/mg tissue weight (median (lQR)), 49% (median inhibition) compared with control vehicle (24 (17-44)). Significant inhibition of ROM production also occurred with FG (196 (32-508), 40%, p=0.05), SE (32 (27-325), 71%, p=0.02) and TCM (25 (16-382), 60%, p=0.02) (all I in 100 dilution), compared with control vehicle (715 (65-1174)). Conclusions: All the herbal remedies tested have antioxidant effects. FG reduces ROM production by inflamed colonic biopsies but unlike the other three materials, is not a free radical scavenger. Their antioxidant action on inflamed colonic mucosa in vitro, suggest that they may be worth further evaluation as possible novel therapies in IBO.
AGAA583
3032 A RANDOMISED DOUBLE BLIND CONTROLLED TRIAL OF HIGH VERSUS LOW LONG CHAIN TRIGLYCERIDE WHOLE PROTEIN FEED IN ACTIVE CROHN'S DISEASE. Keith Leiper, Jenny T. Woolner, Tracy 1. Parker, Martine van der Vleit, Monica M. Mullan, Simon Fear, Jonathan M. Rhodes, John O. Hunter, Univ of Liverpool, Liverpool, United Kingdom; Acad Hosp, Cambridge, United Kingdom; Roy Castle Intl Ctr for Lung Cancer Research, Liverpool, United Kingdom. Background Some trials of polymeric and elemental diets have shown equivalent therapeutic efficacy to corticosteroids in active Crohn's disease (CD). However overall the results of trials with enteral feeds have been variable with response rates between 22% and 82%. Two independent metanalyses of elemental, peptide and whole protein feeds have shown a strong negative correlation between remission rate of CD and the long chain triglyceride (LCT) content of the feed, particularly when LCT contributes more than 15% of the total energy of the diet. We therefore tested the hypothesis that a single whole protein feed with LCT supplying 5% of the total energy would be more effective in inducing remission than a feed with LCT supplying 30% of total energy. Methods A randomised controlled double blind trial of high versus low LCT enteral feed was performed in patients with active CD. Fifty four patients with active Crohn s disease (CDAI >200, CRP > IOmgll) were randomised to a high or low LCT whole protein feed for 3 weeks taken by mouth or by nasogastric tube feeding. The total amount of energy supplied by fat was identical in the two feeds. Remission was defined as a CDAI ::;150 and response as a fall in CDAI of >70 points or a fall in CRP to less than IOmgll. There were no significant differences between the two dietary groups in baseline CDAI, CRP, weight, age or site of disease. Statistical analysis was by Wilcoxon rank sum test, Welch-modified two sample t-test, and Fisher s exact test. Results Overall remission rate was 25% for low LCT diet and 33% for high LCT diet (p=0.8). Thirty one percent (19/54) of patients withdrew before three weeks because of inability to tolerate the diet with no differences in withdrawal rate between the two diets. Excluding patients unable to tolerate the diet, the remission rates were 65% for low LCT and 68% for high LCT (p= 1). Including all patients the overall response defined as a fall in CDAI of >70 points was 33% for low LCT and 52% for high LCT diet (p=0.27). A reduction in CRP to less than 10 was achieved in 30% in the low LCT and 33% in the high LCT group (p=I). Discussion This trial has shown no difference in the response or remission rates between low and high LCT whole protein enteral diets in active CD. The cause of the apparently strong inverse correlation between LCT content of diet and response in active CD remains unclear but may be due to some other component of the feed
3033 RISK OF SURGERY AND THE VIENNA CLASSIFICATION OF CROHN'S DISEASE. Vera Leotta, Giustina Milite, Maddalena Zippi, Alessandra Mancini, Giuseppina Cadau, Angelo Viscido, Renzo Caprilli, Dept of Gastroenterology, Rome, Italy. The classification of patients with Crohn's disease, according to Vienna Classification (1998) considers three different variables (ALB): Age at diagnosis (Al<40 years; A2~40 years), Location oflesions (Ll terminal ileum, L2 colon, L3 ileo-colon, U upper GI) and Behavior of disease (B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating). Aim. To evaluate in our series of CO patients the need of surgery respect to the different variables of the Vienna classification. Patients and Methods. We considered 445 patients with Crohn's Disease consecutively seen at the G1 unit of the University of Rome "La Sapienza" from 1978 to 1999 and in regular follow-up for at least I year (range I to 21 years). Of these, 265 patients (59,5%) had been submitted to surgery. The occurrence of surgery was evaluated respect to each subgroup of the ALB Classification and to family history. Chi-square test was used for the analisys. Results. No difference was found for the incidence of surgery respect to age at diagnosis. The Ileal and Ileocolonic locations were associated with higher frequence of surgery respect to Colonic and Upper GI locations ( 62% and 65% vs 32% and 39% respectively). Considering colonic location the reference category, odds ratio (OR) for surgery in patients with ileal and ileocolonic disease were 3,55 (95% CI 1,61-7,52) and 3,93 (95% CI 1,76-8,91) respectively. Concerning behavior, the Non-stricturing Nonpenetrating disease was associated with a lower incidence of surgery, compared to Stricturing and Penetrating diseases (17%, 65%, and 69% respectively). Considering the Non-stricturing Non-penetrating the reference group, the OR for surgery in patients with Stricturing or Penetrating disease were 8,75 (95% CI 4,10-19) and 10,49 (95% CI 5,08-19,49), respectively. The incidence of surgery was 68% in patients with and 58% in patients without positive family history for IBD. The figure was not significant. Conclusions. The results of this study confirm that ileal and ileocolonic location as well as penetrating disease are associated with higher need for surgery. However, unlike other observations, age at diagnosis and positive family history for IBD were not associated with increased risk for surgery.
Conclusions: These findings suggest that protective effect caused by ES enemas would be mediated by endogenous PGs via COX-I. Thus, ESS enemas may be a good candidate for clinical application because of its preventive effect on acute aggravation of colitis in IBD patients.
3030 ANO·RECTAL FUNCTION AND HISTOLOGICAL CHANGES AF· TER ILEO NEO·RECTAL ANASTOMOSIS, AN ALTERNATIVE PROCEDURE TO THE ILEO·ANAL POUCH. Gunnar I. Andriesse, Marguerite E. Schipper, Louis M. Akkermans, Hein G. Gooszen, Theo 1. Vroonhoven, Cees 1. Laarhoven, Univ Med Ctr, Utrecht, Netherlands. The Ileo Neo-Rectal Anastomosis (lNRA) is an alternative restorative procedure for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) and has been developed in order to reduce the high pouch-related complication (15-35%) and failure rate (6.5%) of the Ileo Pouch-Anal Anastomosis (IPAA). In contrast to IPAA the ano-rectum is preserved and the rectal mucosa is excised and replaced by healthy, vascularised, ileal mucosa. The ultimate purpose, establishment of a compliant neo-rectal reservoir with a concordant low defecation frequency and full continence in the long-term is being addressed in this presentation. In 12 patients (10 UC + 2 FAP) an INRA was performed after subtotal colectomy, with a temporary diverting ileostomy for three months. Anorectal function was tested preoperatively and up to a median of 16 months postoperatively (range 12-22 months). The first sensation, urge sensation, capacity, compliance and anorectal electrosensibility were measured. Anal and rectal ultrasound were carried out to assess the transmural architecture of the neo-rectum. Furthermore histological aspects of neo-rectal mucosa ingrowth and maturation were assessed. The INRA procedure was successfully performed in all patients. Ano-rectal function tests revealed no change in anal sphincter resting (median 8 (6-13) kPa) and squeeze pressure (median 18 (7-35) kPa). Rectal capacity temorarily decreased considerably after INRA, but increased up to normal levels in 12 months (median 108 (56-300) vs 157 (130-225) ml, respectively). This is in accordance with increasing compliance of the neorectum and decreasing stoolfrequency. Anal electrosensibility was unchanged after INRA (median 7 (4-14) rnA), but rectal electrosensibility decreased from median 26 rnA (16-75) to 46 rnA (13-99). Ultrasound showed no structural damage to the anal sphincter and an anatomically normal intestinal wall. Histology showed villus atrophy and a mixed active and chronic inflammatory infiltrate at 6 weeks with recovery in time. At 6 months the villus architecture was restored with an intact goblet cell population and brush border and dissapearance of the inflammatory infiltrate. Although during the INRA procedure the anorectum is manipulated to great extend, anorectal function is perserved. Anorectal function, as well as the functional result after INRA are comparable to IPAA. Ileal mucosa transplantation is feasible with development of healthy neorectal mucosa.
3031 HERBAL THERAPIES USED BY PATIENTS FOR INFLAMMATORY BOWEL DISEASE ARE ANTIOXIDANT IN VITRO. Louise Langmead, Nadine Banna, Suat Loo, David S. Rampton, St Bartholomew's and The Royal London Sch of Medicine, London, United Kingdom. Background: Herbal remedies used by patients for the treatment of inflammatory bowel disease (mD) include Aloe vera gel (AV), the mucilaginous pulp of the leaves of the Aloe Barbadensis Miller plant, fenugreek (FG), an Ayurvedic therapy, slippery elm (SE) made from the bark of the slippery elm tree, and mixtures of herbs prescribed as Traditional Chinese Medicine (TCM). Each is claimed to soothe inflamed intestine. Reactive oxygen metabolites (ROM) are produced by inflamed colonic mucosa and may be pathogenic in IBO. Aminosalicylates are antioxidant and other such agents may have a therapeutic role in IBD. Aim: To assess the antioxidant effects of herbal remedies in a cell-free oxidant-generating system and in inflamed human colorectal biopsies. Methods: Luminol-enhanced chemiluminescence (CL) was used to detect ROM production by xanthine/xanthine oxidase, and from mucosal biopsies from patients with active ulcerative colitis incubated for 40 minutes in the presence of AV, FG, SE, TCM or inert vehicle. Results: In the cell-free system serial dilutions of AV (IC50= 1 in 100), SE (1 in 5000) and TCM (1 in 10000), but not FG, showed dose-dependent ROM scavenging effects. ROM release from inflamed mucosal biopsies was reduced after incubation with AV diluted 1 in 50 (17 (8-18) cps/mg tissue weight (median (lQR)), 49% (median inhibition) compared with control vehicle (24 (17-44)). Significant inhibition of ROM production also occurred with FG (196 (32-508), 40%, p=0.05), SE (32 (27-325), 71%, p=0.02) and TCM (25 (16-382), 60%, p=0.02) (all I in 100 dilution), compared with control vehicle (715 (65-1174)). Conclusions: All the herbal remedies tested have antioxidant effects. FG reduces ROM production by inflamed colonic biopsies but unlike the other three materials, is not a free radical scavenger. Their antioxidant action on inflamed colonic mucosa in vitro, suggest that they may be worth further evaluation as possible novel therapies in IBO.
AGAA583
3032 A RANDOMISED DOUBLE BLIND CONTROLLED TRIAL OF HIGH VERSUS LOW LONG CHAIN TRIGLYCERIDE WHOLE PROTEIN FEED IN ACTIVE CROHN'S DISEASE. Keith Leiper, Jenny T. Woolner, Tracy 1. Parker, Martine van der Vleit, Monica M. Mullan, Simon Fear, Jonathan M. Rhodes, John O. Hunter, Univ of Liverpool, Liverpool, United Kingdom; Acad Hosp, Cambridge, United Kingdom; Roy Castle Intl Ctr for Lung Cancer Research, Liverpool, United Kingdom. Background Some trials of polymeric and elemental diets have shown equivalent therapeutic efficacy to corticosteroids in active Crohn's disease (CD). However overall the results of trials with enteral feeds have been variable with response rates between 22% and 82%. Two independent metanalyses of elemental, peptide and whole protein feeds have shown a strong negative correlation between remission rate of CD and the long chain triglyceride (LCT) content of the feed, particularly when LCT contributes more than 15% of the total energy of the diet. We therefore tested the hypothesis that a single whole protein feed with LCT supplying 5% of the total energy would be more effective in inducing remission than a feed with LCT supplying 30% of total energy. Methods A randomised controlled double blind trial of high versus low LCT enteral feed was performed in patients with active CD. Fifty four patients with active Crohn s disease (CDAI >200, CRP > IOmgll) were randomised to a high or low LCT whole protein feed for 3 weeks taken by mouth or by nasogastric tube feeding. The total amount of energy supplied by fat was identical in the two feeds. Remission was defined as a CDAI ::;150 and response as a fall in CDAI of >70 points or a fall in CRP to less than IOmgll. There were no significant differences between the two dietary groups in baseline CDAI, CRP, weight, age or site of disease. Statistical analysis was by Wilcoxon rank sum test, Welch-modified two sample t-test, and Fisher s exact test. Results Overall remission rate was 25% for low LCT diet and 33% for high LCT diet (p=0.8). Thirty one percent (19/54) of patients withdrew before three weeks because of inability to tolerate the diet with no differences in withdrawal rate between the two diets. Excluding patients unable to tolerate the diet, the remission rates were 65% for low LCT and 68% for high LCT (p= 1). Including all patients the overall response defined as a fall in CDAI of >70 points was 33% for low LCT and 52% for high LCT diet (p=0.27). A reduction in CRP to less than 10 was achieved in 30% in the low LCT and 33% in the high LCT group (p=I). Discussion This trial has shown no difference in the response or remission rates between low and high LCT whole protein enteral diets in active CD. The cause of the apparently strong inverse correlation between LCT content of diet and response in active CD remains unclear but may be due to some other component of the feed
3033 RISK OF SURGERY AND THE VIENNA CLASSIFICATION OF CROHN'S DISEASE. Vera Leotta, Giustina Milite, Maddalena Zippi, Alessandra Mancini, Giuseppina Cadau, Angelo Viscido, Renzo Caprilli, Dept of Gastroenterology, Rome, Italy. The classification of patients with Crohn's disease, according to Vienna Classification (1998) considers three different variables (ALB): Age at diagnosis (Al<40 years; A2~40 years), Location oflesions (Ll terminal ileum, L2 colon, L3 ileo-colon, U upper GI) and Behavior of disease (B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating). Aim. To evaluate in our series of CO patients the need of surgery respect to the different variables of the Vienna classification. Patients and Methods. We considered 445 patients with Crohn's Disease consecutively seen at the G1 unit of the University of Rome "La Sapienza" from 1978 to 1999 and in regular follow-up for at least I year (range I to 21 years). Of these, 265 patients (59,5%) had been submitted to surgery. The occurrence of surgery was evaluated respect to each subgroup of the ALB Classification and to family history. Chi-square test was used for the analisys. Results. No difference was found for the incidence of surgery respect to age at diagnosis. The Ileal and Ileocolonic locations were associated with higher frequence of surgery respect to Colonic and Upper GI locations ( 62% and 65% vs 32% and 39% respectively). Considering colonic location the reference category, odds ratio (OR) for surgery in patients with ileal and ileocolonic disease were 3,55 (95% CI 1,61-7,52) and 3,93 (95% CI 1,76-8,91) respectively. Concerning behavior, the Non-stricturing Nonpenetrating disease was associated with a lower incidence of surgery, compared to Stricturing and Penetrating diseases (17%, 65%, and 69% respectively). Considering the Non-stricturing Non-penetrating the reference group, the OR for surgery in patients with Stricturing or Penetrating disease were 8,75 (95% CI 4,10-19) and 10,49 (95% CI 5,08-19,49), respectively. The incidence of surgery was 68% in patients with and 58% in patients without positive family history for IBD. The figure was not significant. Conclusions. The results of this study confirm that ileal and ileocolonic location as well as penetrating disease are associated with higher need for surgery. However, unlike other observations, age at diagnosis and positive family history for IBD were not associated with increased risk for surgery.