Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study.

OBJECTIVE: Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. PATIENTS AND METHODS: All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. RESULTS: 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group. CONCLUSIONS: UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.

Magnetization transfer ratio for the assessment of perianal fistula activity in Crohn's disease.

OBJECTIVES: Assessment of perianal fistulas is important to guide management of Crohn's disease (CD). Our objectives were to analyze the feasibility of magnetization transfer (MT) imaging to assess fistulas and to evaluate its contribution in assessing disease activity. METHODS: During 15 months, all patients referred for perianal fistulas in CD underwent 3T-MRI including diffusion, T2/T1-weighted gadolinium-enhanced sequences and MT sequences (one with an off-resonance saturation pulse of 800 and one with 1200 Hz). We collected Van Assche score, fistula activity signs by analyzing T2, diffusion and contrast enhancement. We calculated MT ratio (MTR) with a ROI in the largest fistula. RESULTS: Twenty-nine patients (mean 34.9 years, range 17-53) were included. Van Assche score was 11.7, range 4-21. In 22 patients, the fistula presented with a bright T2 and diffusion signal with contrast enhancement, and was characterized as active. Mean MTR was respectively 47.2 (range 12-68) and 34.3 (range 11-57) at 800 and 1200 Hz. MTR at 800 Hz was significantly lower in non-active (34, range 12-55) than in active fistulas (51, range 24-68) (p < 0.02). CONCLUSIONS: MTR is feasible for the assessment of fistulas in CD and in the future could be used to help identify active and non-active fistulas. KEY POINTS: • MTR is feasible for the assessment of perianal fistulas in CD. • MT allows quantitative imaging of perianal fistula activity in CD. • MTR could be used to help identify active and non-active fistulas in CD.

Magnetic resonance colonography in severe attacks of ulcerative colitis.

OBJECTIVES: To evaluate the ability of MR colonography (MRC) to detect lesions in severe attacks of ulcerative colitis (UC) and to assess its concordance with rectosigmoidoscopy. METHODS: Eighteen patients underwent MRC and rectosigmoidoscopy. MRC consisted of a water-filled colonic procedure followed by T1/T2w images. Image quality was recorded. Inflammatory lesions and the existence of signs of severity were analysed. We calculated MR accuracy in the diagnosis of inflammatory lesions, as well as per segment and per patient concordance depending on the presence or absence of severe lesions. RESULTS: The MR image quality of the 108 segments was satisfactory. Endoscopy was used to study 36 segments (rectum and sigmoid). MRC had a positive predictive value of 100% and a sensitivity of 64% in the diagnosis of inflammatory lesions. Concordance for the diagnosis of severe lesions was excellent for the rectum (k = 0.85) and good for the sigmoid (k = 0.64). MRC diagnosed signs of severity in all patients affected at endoscopy. MRC also disclosed signs of severity located higher in the colon in four patients with nonsevere lesions at rectosigmoidoscopy. CONCLUSIONS: MRC can accurately diagnose inflammatory lesions in severe attacks of UC and significantly correlates with rectosigmoidoscopy in the diagnosis of severe lesions.

Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study.

INTRODUCTION: Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. METHODS: A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. RESULTS: Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. CONCLUSIONS: In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

A fulminant colitis index greater or equal to 8 is not predictive of colectomy risk in infliximab-treated moderate-to-severe ulcerative colitis attacks.

INTRODUCTION: In severe attacks of ulcerative colitis (UC) treated with intravenous corticosteroids, a fulminant colitis index (FCI) greater or equal to 8 has been associated with a greater likelihood of colectomy (72 vs 16% with an FCI<8). This retrospective study aimed to assess the accuracy of such an association in infliximab-treated patients with moderate-to-severe bouts of UC. PATIENTS AND METHODS: The study was based on the medical files of 43 patients who had received at least one infusion of infliximab to treat moderate-to-severe UC (partial Mayo Clinic score). Remission and clinical response were also assessed using the partial Mayo score. The accuracy of an FCI greater or equal to 8 to predict the likelihood of colectomy was assessed by calculating the sensitivity, specificity, positive and negative predictive values, Yule's Q coefficient, Youden's index and statistical significance (Chi(2) test). RESULTS: After treatment with infliximab, 10 patients were in remission (23.3%), 21 (48.8%) had a clinical response, four (9.3%) had treatment failure (without, however, requiring colectomy) and eight (18.6%) had a colectomy. Calculation of the above-mentioned indicators revealed that an FCI greater or equal to 8 was not an indicator of the risk of colectomy in this patient population, and found that only an FCI greater or equal to 16 was statistically significant. However, low values for sensitivity, positive predictive value and Youden's index preclude the clinical application of this latter result. CONCLUSION: In patients treated with infliximab for moderate-to-severe UC attacks, the FCI is not a predictor of colectomy. In such patients, the factors predictive of a response to treatment or likelihood of colectomy, currently acknowledged with corticosteroid treatment, need to be further assessed for infliximab treatment.

Post-operative complications in elderly onset inflammatory bowel disease: a population-based study.

BACKGROUND: IBD diagnosed after the age of 60 is increasing. Data on post-operative complications in elderly onset IBD are scarce. AIM: To describe the incidence of and factors associated with post-operative complications in elderly onset IBD, diagnosed after the age of 60. METHODS: Using EPIMAD Cohort (1988-2006), among 841 incident IBD patients, 139 (17%) underwent intestinal surgery, including 100 Crohn's disease (CD) and 39 ulcerative colitis (UC). RESULTS: After a median post-operative follow-up of 6 years (2-10), 50 (36%) patients experienced at least 1 complication with a total of 69. During the first 30 post-operative days, the mortality rate was 4%. Thirty-two early complications (<30 days) were observed in 23 patients (17%), with 15 infectious, without significant difference between CD and UC. More than half early post-operative complications (n = 19, 59%) were severe (>grade 2) without significant difference between CD and UC (P = 0.28). Thirty-seven long-term adverse effects of surgical therapy (≥30 days) were observed in 33 patients (24%). Multivariate analysis found (1) acute severe colitis (OR = 7.84 [2.15-28.52]) and emergency surgery (OR = 4.46 [1.75-11.36]) were associated with early post-operative complications, and (2) Female gender (HR = 2.10 [1.01-4.37]) and delay before surgery >3 months (HR = 2.09 [1.01-4.31]) with long-term adverse effects of surgical therapy. CONCLUSIONS: One-third of elderly IBD patients experienced at least 1 post-operative complication. Half of the early complications were severe, and infectious. Emergency surgery was the key driver for post-operative complication.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.

Incidence and Phenotype at Diagnosis of Very-early-onset Compared with Later-onset Paediatric Inflammatory Bowel Disease: A Population-based Study [1988-2011].

BACKGROUND AND AIMS: Very-early-onset inflammatory bowel disease [VEO-IBD] is a form of IBD that is distinct from that of children with an older onset. We compared changes over time in the incidence and phenotype at diagnosis between two groups according to age at IBD diagnosis: VEO-IBD diagnosed before the age of 6 years, and early-onset IBD [EO-IBD] diagnosed between 6 and 16 years of age. METHODS: Data were obtained from a cohort enrolled in a prospective French population-based registry from 1988 to 2011. RESULTS: Among the 1412 paediatric cases [< 17 years], 42 [3%] were VEO-IBD. In the VEO-IBD group, the incidence remained stable over the study period. In contrast, the incidence of EO-IBD increased from 4.4/105 in 1988-1990 to 9.5/105 in 2009-2011 [+116%; p < 10-4]. Crohn's disease [CD] was the most common IBD, regardless of age, but ulcerative colitis [UC] and unclassified IBD were more common in VEO-IBD cases [40% vs 26%; p = 0.04]. VEO-IBD diagnosis was most often performed in hospital [69% vs 43%; p < 10-3]. Rectal bleeding and mucous stools were more common in patients with VEO-IBD, whereas weight loss and abdominal pain were more frequent in those with EO-IBD. Regarding CD, isolated colonic disease was more common in the VEO-IBD group [39% vs 14%; p = 0.003]. CONCLUSIONS: In this large population-based cohort, the incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific clinical presentation. These results suggest a probable genetic origin for VEO-IBD, whereas the increase in EO-IBD might be linked to environmental factors.

Cholangiopathy in critically ill patients surviving beyond the intensive care period: a multicentre survey in liver units.

BACKGROUND: The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay. AIM: To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay. METHODS: The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease. RESULTS: Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests. CONCLUSIONS: In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

BACKGROUND: We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. AIMS: To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. METHODS: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. RESULTS: At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.

Relevance of 3D Cholangiography and Transient Elastography to Assess Cystic Fibrosis-Associated Liver Disease?

Background. Cystic fibrosis-associated liver disease (CFLD) is a major cause of death. The objective of our retrospective study was to describe the relevance of magnetic resonance imaging (MRI) and liver stiffness measurement (LSM) for CFLD evaluation. Methods. All cystic fibrosis adult patients evaluated by MRI and LSM were included. MR signs of portal hypertension (PHT), dysmorphia, or cholangitis were collected and LSM expressed in kPa and Metavir. Results. Of 25 patients, 52% had abnormal MRI. Median LSM was 5.7 kPa (3.4-9.9). Three patients had F2 score and one had F3 score. In patients with PHT, LSM was 7.85 kPa (3.7-9.9) compared to 5 (3.4-7.5) in others, p = 0.02. In patients with abnormal liver function tests, 50% had increased LSM (≥F2), whereas 94% with normal tests had normal LSM (p = 0.04). Seven patients had abnormal MRI despite normal ultrasonography. Conclusions. MRI and LSM provide useful information on CFLD and may help to screen patients with PHT.

Fistula Plug in Fistulising Ano-Perineal Crohn's Disease: a Randomised Controlled Trial.

BACKGROUND AND AIMS: Anal fistula plug [AFP] is a bioabsorbable bioprosthesis used in ano-perineal fistula treatment. We aimed to assess efficacy and safety of AFP in fistulising ano-perineal Crohn's disease [FAP-CD]. METHODS: In a multicentre, open-label, randomised controlled trial we compared seton removal alone [control group] with AFP insertion [AFP group] in 106 Crohn's disease patients with non- or mildly active disease having at least one ano-perineal fistula tract drained for more than 1 month. Patients with abscess [collection ≥ 3mm on magnetic resonance imaging or recto-vaginal fistulas were excluded. Randomisation was stratified in simple or complex fistulas according to AGA classification. Primary end point was fistula closure at Week 12. RESULTS: In all, 54 patients were randomised to AFP group [control group 52]. Median fistula duration was 23 [10-53] months. Median Crohn's Disease Activity Index at baseline was 81 [45-135]. Fistula closure at Week 12 was achieved in 31.5% patients in the AFP group and in 23.1 % in the control group (relative risk [RR] stratified on AGA classification: 1.31; 95% confidence interval: 0.59-4.02; p = 0.19). No interaction in treatment effect with complexity stratum was found; 33.3% of patients with complex fistula and 30.8% of patients with simple fistula closed the tracts after AFP, as compared with 15.4% and 25.6% in controls, respectively [RR of success = 2.17 in complex fistula vs RR = 1.20 in simple fistula; p = 0.45]. Concerning safety, at Week 12, 17 patients developed at least one adverse event in the AFP group vs 8 in the controls [p = 0.07]. CONCLUSION: AFP is not more effective than seton removal alone to achieve FAP-CD closure.

[Spontaneous intrahepatic hematoma: an unexpected etiology]. / Hématome intra-hépatique spontané : une étiologie inattendue.

INTRODUCTION: Diagnosis of AL amyloidosis can be complicated by the diversity and the absence of specificity of symptoms. CASE REPORT: We report a patient who presented with a non-traumatic hepatic hematoma, leading to the discovery of hepatic amyloidosis secondary to probable multiple myeloma. The originality of our report lies in the discovery of two acquired abnormalities of haemostasis: a factor X deficiency and an acquired von Willebrand syndrome, by a likely inhibitor. CONCLUSION: Our case report is a reminder of the importance of haemostasis analysis in AL amyloidosis.

How do fiber-supplemented formulas affect antroduodenal motility during enteral nutrition? A comparative study between mixed and insoluble fibers.

BACKGROUND: Fiber supplementation during enteral nutrition has been recommended, but the effect of soluble compared with insoluble fiber supplements on antroduodenal motility is unknown. OBJECTIVE: The objective of this study was to compare antroduodenal motor patterns in 8 healthy volunteers during and after gastric infusion of 3 different diets: a fiber-free diet, an insoluble-fiber diet, and a mixed-fiber diet (50% soluble fiber and 50% insoluble fiber). DESIGN: Manometric studies with the 3 different diets (2100 kJ) were performed in random order. Antroduodenal motility was monitored continuously for 6 h by using a pneumohydraulic system to calculate the number, amplitude, and duration of the pressure waves; the area under the curve (AUC); and the percentage of time occupied by motor activity before, during, and after each type of infusion. Variations in antral areas were measured by ultrasonography. RESULTS: The gastric motor response was significantly higher, whatever the diet, in the distal antral recording site than in the 2 more proximal sites. In the proximal but not the distal antrum, the number of waves, the AUC, and the percentage of time occupied by motor activity were higher (P: < 0.04) with the mixed-fiber than with the insoluble-fiber diet. No significant differences in variations of antral area were observed among the 3 diets. In the duodenum, motor variables were not significantly different among the 3 diets. CONCLUSIONS: A gastric infusion induced a greater motor response in the distal than in the proximal antrum. A mixed-fiber diet was associated with significantly greater proximal antral motility than was an insoluble-fiber diet. There was no significant difference among the 3 formulas in duodenal motor variables or in variations in antral area as measured by ultrasound.

Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation.

The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty-four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high-amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 +/- 11.6 vs 1 +/- 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food-induced colonic motor response and significantly lower colonic activity in transverse colon (374 +/- 1220 vs 3249 +/- 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 +/- 6364 vs 88780 +/- 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.

Does the supplementation of the formula with fibre increase the risk of gastro-oesophageal reflux during enteral nutrition? A human study.

BACKGROUND & AIMS: Fibre-supplements in enteral feeding could increase the risk of gastro-oesophageal reflux (GOR). The aim of this study was to assess in humans the physiological effects of the supplementation of the enteral diet with different types of dietary fibre on gastro-oesophageal reflux episodes, gastric acidity and gastric emptying. METHODS: pH profiles were compared in 12 healthy volunteers between three different formula (500 kcal, 250 mL x h-1) delivered in a random order and containing either no fibre, either soy polysaccharide fibre only or mixed fibre from pea and inuline. Enteral diets were instilled through a nasogastric tube. Oesophageal and gastric pH recordings were combined with the ultrasound measurement of gastric antral area during the infusion. RESULTS: More GOR were observed with a fibre-free diet (median 4, range 1-10) than with a mixed (median 1.5, range 0-5) (P=0.04) or soy polysaccharide fibre (median 1.5, range 0-5) (P=0.04) diet. The median duration of GOR was longer with the mixed fibre (median 3.6, range 1.8-7.2) than with the fibre-free diet (mean 1.8 min, range 1-3.6) (P<0.05). The number of GOR episodes lasting more than 5 min, the duration of the longest GOR and the percent of time under pH 4 were not significantly different with the three diets. The intragastric pH profile and the ultrasound antral area were not different with all three diets. CONCLUSIONS: Addition of fibre to the enteral formula had limited effects on the onset of GOR episodes. It decreased the number of GOR but increased their duration. These effect were more pronounced with the formula containing soluble fibre. At variance, the addition of fibre had no significant effect on gastric emptying and gastric acid secretion.

Low levels of glutathione in endoscopic biopsies of patients with Crohn's colitis: the role of malnutrition.

BACKGROUND AND AIMS: During active Crohn's disease, generation of free radicals is increased, and nutritional depletion is frequent. We investigated the glutathione concentration of the colonic mucosa in biopsies from patients with active Crohn's colitis depending on nutritional status. METHODS: Endoscopic biopsies were taken in 10 well-nourished control patients, and 18 patients with active Crohn's disease (11 well-nourished, seven malnourished with a recent weight loss > 10 %). Colonic biopsies were taken from healthy and inflamed mucosa and analysed for total glutathione concentration. RESULTS: Mucosal glutathione concentration (nmol/mg wet tissue) was lower in patients with active colitis both in diseased and healthy mucosa as compared with controls (1.89 +/- 0.39, 2.08 +/- 0.4 and 6.69 +/- 4. 94, respectively, P< 0.05). Mucosal glutathione was lower in healthy mucosa from malnourished versus well-nourished patients: 1.8 +/- 0.2 vs 2.3 +/- 0.37 (P= 0.02). CONCLUSIONS: Mucosal glutathione is markedly lower in active Crohn's colitis, even in healthy mucosa; glutathione depletion tends to be more severe in malnourished patients. Glutathione depletion may be related in part to malnutrition and contribute to a prolonged evolution of disease and could be a target for pharmacological and nutritional support.