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.

Biliary stenting is not a prerequisite to endoscopic placement of duodenal covered self-expandable metal stents.

BACKGROUND: Duodenal covered self-expandable metal stent (cSEMS) can be used in malignant or benign gastroduodenal obstruction. The need for biliary stenting in patients with no concomitant biliary stricture, before duodenal cSEMS placement, remains unknown. The aim of this study was to determine whether cSEMS placement is responsible for biliary obstruction. METHODS: This is a single-center, retrospective, case-controlled study, including 106 patients with symptomatic gastric outlet obstruction or duodenal fistula who received a covered nitinol duodenal stent by using through-the-scope/over-the-wire placement procedure. The main outcome measurement was the occurrence comparison of jaundice and bilirubin level, between patients with previous or concomitant biliary stenting (cSEMS + BS group), and patients with no biliary stent (cSEMS group) during an observational period of 90 days. RESULTS: Hundred and six patients underwent cSEMS placement between June 2005 and March 2014: 53 in the cSEMS group (58% male, mean age 66.4 ± 13.3 years) and 53 in cSEMS + BS group (60% male, mean age 70.4 ± 11.6 years). The obstruction was due to cancer in 45% in cSEMS group and 87% in cSEMS + BS group. No case of jaundice was reported in the cSEMS group or in the cSEMS + BS group. In cSEMS group, the mean bilirubin level (µmol/L ± SD) was 8.0 ± 4 at baseline and 8.5 ± 4.6 at day 10, while in the cSEMS + BS group it was 91.4 ± 108 at baseline and 35.3 ± 39 at day 10 (p < 0.01). Patients from the two groups were matched on age, gender and bilirubin level at baseline. Evolution of bilirubinemia was +0.98 ± 2.76 µmol/L in experimental group and +0.39 ± 522 µmol/L in the control group (p = 0.34). No significant difference was observed between the two groups in term of technical success, clinical effectiveness, migration and other complications. CONCLUSIONS: Previous biliary stenting is not required before endoscopic covered duodenal stent placement in patients with no associated biliary obstruction. Prospective studies are needed.

Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn's disease: validation of quantitative index of activity.

OBJECTIVES: Magnetic resonance imaging (MRI) allows accurate assessment of Crohn's disease (CD), but requires gadolinium injection. Diffusion-weighted (DW)-MRI yields comparable performances in small bowel CD. We compared the accuracy of DW-MR enterocolonography (MREC) and the magnetic resonance index of activity (MaRIA), and performed an external validation of the Clermont score in assessing inflammation in CD. METHODS: This was an observational prospective study of a single-center cohort. A total of 130 CD patients underwent consecutively MREC with gadolinium injection and DWI sequences between July 2011 and December 2012. RESULTS: Of the 848 evaluated segments (small bowel=352, colon/rectum=496), 175 (20.6%) were active (small bowel=111, colon/rectum=64) defined as MaRIA ≥7. Using a receiver operating characteristic (ROC) curve, we determined an apparent coefficient of diffusion (ADC) threshold of 1.9 × 10(-3) mm(2)/s that yielded a sensitivity and a specificity in discriminating active from nonactive CD of 96.9% and 98.1%, respectively, for the colon/rectum, and 85.9% and 81.6%, respectively, for the ileum. ADC was better correlated to MaRIA ≥7 than related contrast enhancement obtained with injected sequences (P<0.001). The Clermont score (=1.646 × bowel thickness-1.321 × ADC+5.613 × edema+8.306 × ulceration+5.039) was highly correlated with the MaRIA (rho=0.99) in ileal CD but not in colonic CD (rho <0.80). Interobserver agreement was high with regard to ADC measurement (correlation >0.9, P<0.001, and concordance >0.9, P<0001). CONCLUSIONS: DW-MREC is a reliable tool to assess inflammation in colonic (ADC) and ileal (Clermont score) CD and its use in daily practice would avoid gadolinium injection.

Long-term follow-up after biliary stent placement for postcholecystectomy bile duct strictures: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic stenting is a recognized treatment of postcholecystectomy biliary strictures. Large multicenter reports of its long-term efficacy are lacking. Our aim was to analyze the long-term outcomes after stenting in this patient population, based on a large experience from several centers in France. METHODS: Members of the French Society of Digestive Endoscopy were asked to identify patients treated for a common bile duct postcholecystectomy stricture. Patients with successful stenting and follow-up after removal of stent(s) were subsequently included and analyzed. Main outcome measures were long-term success of endoscopic stenting and related predictors for recurrence (after one stenting period) or failure (at the end of follow-up). RESULTS: A total of 96 patients were eligible for inclusion. The mean number of stents inserted at the same time was 1.9±0.89 (range 1-4). Stent-related morbidity was 22.9% (n=22). The median duration of stenting was 12 months (range 2-96 months). After a mean follow-up of 6.4±3.8 years (range 0-20.3 years) the overall success rate was 66.7% (n=64) after one period of stenting and 82.3% (n=79) after additional treatments. The mean time to recurrence was 19.7±36.6 months. The most significant independent predictor of both recurrence and failure was a pathological cholangiography at the time of stent removal. CONCLUSION: Endoscopic stenting helps to avoid surgery in more than 80% of patients bearing postcholecystectomy common bile duct strictures. However, a persistent anomaly on cholangiography at the time of stent removal is a strong predictor of recurrence and may lead to consideration of surgery.

Multidrug-resistant Klebsiella pneumoniae outbreak after endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: Infection is a recognized complication of endoscopic retrograde cholangiopancreatography (ERCP). We describe the epidemiologic and molecular investigations of an outbreak of ERCP-related severe nosocomial infection due to KLEBSIELLA PNEUMONIAE producing extended-spectrum beta-lactamase (ESBL). PATIENTS AND METHODS: We conducted epidemiologic and molecular investigations to identify the source of the outbreak in patients undergoing ERCP. We carried out reviews of the medical and endoscopic charts and microbiological data, practice audits, surveillance cultures of duodenoscopes and environmental sites, and molecular typing of clinical and environmental isolates. RESULTS: Between December 2008 and August 2009, 16 patients were identified post-ERCP with KLEBSIELLA PNEUMONIAE that produced extended-spectrum beta-lactamase type CTX-M-15. There were 8 bloodstream infections, 4 biliary tract infections, and 4 cases of fecal carriage. The microorganism was isolated only from patients who had undergone ERCP. Environmental investigations found no contamination of the washer-disinfectors or the surfaces of the endoscopy rooms. Routine surveillance cultures of endoscopes were repeatedly negative during the outbreak but the epidemic strain was finally isolated from one duodenoscope by flushing and brushing the channels. Molecular typing confirmed the identity of the clinical and environmental strains. Practice audits showed that manual cleaning and drying before storage were insufficient. Strict adherence to reprocessing procedures ended the outbreak. CONCLUSIONS: The endoscopes used for ERCP can act as a reservoir for the emerging ESBL-producing K. PNEUMONIAE. Regular audits to ensure rigorous application of cleaning, high-level disinfection, and drying steps are crucial to avoid contamination.

Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

[Gastroduodenal ulcer before and after Helicobacter pylori]. / Ulcère gastroduodénal: avant et après Helicobacter pylori.

Before the discovery of Helicobacter pylori, ulcer disease was considered as the result of a conflict between gastric acid and pepsin, on one side, and protection afforded by gastric mucosal barrier, on the other side. The discovery of H. pylori by Marshall and Warren in 1982 overthrew this conception and revealed ulcer disease mainly as an infectious disease. H. pylori eradication with an appropriate triple therapy is now considered as the gold standard treatment of gastroduodenal ulcer. The pathogenic role of H. pylori lies far beyond ulcer disease since H. pylori is looked as involved in nonulcer dyspepsia, nonsteroidal anti-inflammatory drug ulcers, gastric cancer, MALT lymphoma and, eventually, oesophageal adenocarcinoma, and nondigestive diseases as cardiovascular diseases. The pandemic nature of the H. pylori infection, particularly within developing countries, combined with emerging resistances to antibiotics make the development of a vaccine a public health necessity. The relationships between the human host and the bacterium remains mostly unknown, some of which could be beneficial.

The epidemiology and virology of hepatitis C virus genotype 5 in central France.

BACKGROUND: We previously reported high prevalence of hepatitis C virus genotype 5a (HCV 5) (14%) in Central France. AIM: To identify the risk factors associated with HCV5 infection and to characterize local HCV5 lineages. METHOD: A case-control study and phylogenetic analysis were conducted. RESULTS: In all, 131 HCV5 and 343 HCV non 5 infected patients were enrolled. No HCV5 patient was born in sub-Saharan Africa and only two were injection drug user. HCV5 contamination was associated with living in a rural area called Vic le Comte (VLC) in non-transfused patients (OR = 17.7), with transfusion in patients living outside VLC (OR = 3.8) and with receiving injections in patients from VLC (OR = 3.1). More than 80% of the patients from outside VLC were contaminated by transfusion and those from VLC mainly by an iatrogenic factor - injections performed before 1972 by the local physician. Phylogenetic analysis of HCV5 isolates evidenced no distinct genetic cluster, but close relationships between the isolates of spouse pairs and between blood donors and recipients. CONCLUSIONS: Our results suggest that HCV5 spread in our district by iatrogenic route before 1972 and then via transfusion to the whole district. Collaborative studies are underway to study viral sequences from different parts of Africa and Europe to estimate the origin of our HCV 5a strains.

Migraine prevalence in inflammatory bowel disease patients: A tertiary-care centre cross-sectional study.

BACKGROUND: Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory conditions that predominately affect the gastrointestinal tract and can induce abdominal pain. Besides, many IBD patients complain about headaches in daily practice. The objective was to assess the prevalence of headaches, including migraines and pain with neuropathic characteristics (NC), in IBD patients compared to historical controls from the general population. METHODS: Overall, 203 consecutive tertiary-care centre patients completed validated self-administered questionnaires and benefitted from a clinical evaluation performed by an IBD physician at the same time. RESULTS: In our cohort, 75% of the patients experienced pain in the previous 3 months. Migraine prevalence was two-fold higher in IBD patients compared to the general population (41% vs. 21.3%, p < 0.001). Migraine was associated with a younger age, female gender and higher depression scores. Although migraine impact was very important for 30% of the patients (61/203), specific acute therapeutics were prescribed in only 22% of cases (18/83). Chronic pain with NC was more frequent than in the general population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the presence of extra-intestinal manifestations (p < 0.001). Abdominal pain concerned 19% of the patients during the previous week and was, as expected, associated with disease activity. CONCLUSIONS: Migraine prevalence is strongly increased in IBD patients followed in tertiary care. A systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics. Further studies are needed to confirm whether migraine should be classified as IBD extra-intestinal manifestations. SIGNIFICANCE: Migraine prevalence was two-fold higher in IBD patients compared to the general population, was generally poorly treated and a systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics.

Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study.

AIM: To assess the rate of sustained virological response in naïve hepatitis C virus-type 5 patients treated by standard interferon or pegylated-interferon [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND METHODS: A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus-5 patients treated with interferon and peg-interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus-5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus-1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098). CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5-infected patients. Sustained virological response seems better in hepatitis C virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of hepatitis C virus-2-3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus-5 patients.

[Natural history of portal cavernoma without liver disease. A single centre retrospective study of 32 cases]. / Évolution naturelle des cavernomes portaux non liés à une hépatopathie. Étude rétrospective monocentrique de 32 observations.

PURPOSE: Portal cavernoma follows a chronic occlusion of the portal vein. The long-term consequences of portal cavernoma are not well known. The objective of this study was to report the aetiology of the portal cavernoma and its natural course after excluding liver diseases causes. METHODOLOGY: A single centre retrospective study based on the data collected from the radiology department of the Clermont-Ferrand hospital was conducted from 2000 to 2011. All the patients for whom an imagery found a portal cavernoma have been looked for excluding the patients having a liver disease whatever the aetiology and the Budd-Chiari syndrome. RESULTS: Thirty-two cases (18 women and 14 men) were selected. The mean age at diagnosis was 54.2 years and the mean follow-up period was 5.4 years. The discovery of a portal cavernoma was incidental for 8 cases. An aetiology was found for 24 cases: it was an haematological aetiology in 15 cases (10 myeloproliferative syndromes, 2 antiphospholid syndromes, 1 thalassemia major, 1 hyperhomocysteinemia, 1 prothrombin gene mutation), a general aetiology in 2 cases (1 coeliac disease, 1 pancreatic neoplasia), and a local inflammation in 7 cases. A dysmorphic aspect of the liver was noticed on medical imaging for 11 out of the 32 cases. A liver biopsy was performed in 4 patients and was normal for all of them. Sixteen patients developed oesophageal varices, 4 patients developed ascites, 3 developed asymptomatic biliary compression by the portal cavernoma, and the patient who had been followed for the longest time (15 years) developed an encephalopathy. CONCLUSION: In addition to its underlying etiology, the prognosis of portal is mainly related to the occurrence of oesophageal varices that may develop during the follow-up of the patients.

Faecal chitinase 3-like 1 is a reliable marker as accurate as faecal calprotectin in detecting endoscopic activity in adult patients with inflammatory bowel diseases.

BACKGROUND: Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). AIM: To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. METHODS: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. RESULTS: In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 µg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 µg/g showing a sensitivity of 86.4% and a specificity of 80.0%. CONCLUSION: Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.

Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects.

BACKGROUND: Impedance-pH monitoring is the most sensitive method for detection and characterization of gastro-oesophageal reflux episodes. Normal values from European subjects are lacking. AIM: To build a database of gastro-oesophageal reflux patterns from French and Belgian healthy subjects. METHODS: Seventy-two healthy subjects (35 men, mean age 35 years, 18-72) underwent 24-h ambulatory impedance-pH studies. Gastro-oesophageal reflux episodes were detected using impedance and characterized by pH as acid, weakly acidic, or weakly alkaline. Analysis was performed visually and effects of age, gender and intra-individual reproducibility were evaluated. RESULTS: The total number of gastro-oesophageal reflux episodes was 44 (25,58,75) of which 59% were acid, 28% were weakly acidic and 10% weakly alkaline. Half of gastro-oesophageal reflux episodes were mixed (liquid/gas) and 22% reached 15 cm above the lower oesophageal sphincter. The bolus clearance time was 11 s while acid was chemically cleared in 34 s. Male gender was associated with increased number and proximal extent of total and acid gastro-oesophageal reflux. Repeated studies in 27 subjects showed good reproducibility for number, acidity and air-liquid composition of reflux (Kendall's W-values = 0.72-0.85). CONCLUSIONS: This study demonstrates good reproducibility of 24-h ambulatory impedance-pH studies and provides values of reflux patterns in healthy subjects for comparisons with European gastro-oesophageal reflux disease patients.

Diffusion-weighted magnetic resonance imaging is effective to detect ileocolonic ulcerations in Crohn's disease.

BACKGROUND: Magnetic resonance entero-colonography enables accurate assessment of ileocolonic Crohn's disease, but the need for bowel cleansing and rectal enema limits considerably its use in daily practice. AIM: We evaluated the accuracy of diffusion-weighted magnetic resonance entero-colonography with neither bowel cleansing nor rectal enema to assess endoscopic activity. METHODS: Forty-four Crohn's disease patients underwent prospectively and consecutively diffusion-weighted magnetic resonance entero-colonography [with apparent diffusion coefficient (ADC) and Clermont score calculation] and ileocolonoscopy [with Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic score for Crohn's Disease (SES-CD) calculation]. RESULTS: Mean ADC was inversely correlated with total CDEIS (ρ = -0.40; P = 0.0067) and total SES-CD (ρ = -0.33; P = 0.032). Considering the 194 segments, ADC was inversely correlated with segmental CDEIS (-0.48; P < 0.001) and segmental SES-CD (-0.44; P < 0.001). ADC values were lower in segments with deep ulcers (1.30 ± 0.23) or superficial ulcerations (1.75 ± 0.64) than in non-ulcerated segments (2.15 ± 0.5) (P = 0.001). Using a receiver operating curve, we determined that segmental ADC <1.42 detected endoscopic deep ulcerations with sensitivity = 0.91 and specificity = 0.83 (Area under the curve = 0.84; P < 0.001). Segmental ADC <1.88 detected endoscopic superficial ulcerations with sensitivity = 0.64 and specificity = 0.75. The segmental ADC values decreased when the ulcerations size increased (P = 0.0001). Clermont score correlated with ileal CDEIS (0.63; P < 0.05) and ileal SES-CD (0.58; P < 0.05). Clermont score was higher in ulcerated segments (23.3 ± 8.4) than in non-ulcerated segments (12.4 ± 10.0) (P = 0.006) and increased with ulcers size (P = 0.012). Clermont score >18.9 detected ulcerations with sensitivity = 0.79 and specificity = 0.73. CONCLUSION: Diffusion-weighted magnetic resonance entero-colonography using apparent diffusion coefficient and Clermont score was effective to indirectly detect endoscopic ulcerations in ileocolonic Crohn's disease.

Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease.

BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 µg/g, 1251.0 µg/g, and 1800.0 µg/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 µg/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal ≥ 200 µg/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 µg/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface.

Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats.

BACKGROUND AND AIMS: Short-chain fatty acid (SCFA) (especially butyrate) enemas are widely used to reduce symptoms associated with human inflammatory bowel disease. The purpose of this study was to evaluate their real effect on colonic sensitivity in rats. METHODS: The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)). RESULTS: Butyrate enemas (40 mM twice daily for 14 days) decreased colonic pain thresholds in control rats; they did not reduce the TNBS-induced hypersensitivity, but on the contrary increased its duration (without modifying the inflammation score). This pronociceptive effect was confirmed in control rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM of a butyrate solution. The other SCFA enemas did not modify the hypersensitivity of rats with colitis and induced proinflammatory effects. CONCLUSIONS: The beneficial effect of SCFA (especially butyrate) enemas on hypersensitivity and inflammation in inflammatory bowel disease is questionable and needs to be thoroughly investigated in humans.

Interaction of indomethacin and naproxen with gastric surface-active phospholipids: a possible mechanism for the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs).

The possibility that the molecular mechanism underlying the topical gastric irritancy of nonsteroidal anti-inflammatory drugs (NSAIDs) may involve alterations in the surface-active properties of gastric phospholipids was investigated. Indomethacin and naproxen were intragastrically administered to rats and the hydrophobicity of the luminal surface of the stomach wall was assessed by contact angle analysis. Both NSAIDs have the ability to attenuate the phospholipid-related hydrophobic properties of the gastric mucosa by more than 80-85% in a dose-dependent fashion. Potential molecular interactions between both NSAIDs and surface-active phospholipids were analyzed using fluorescent probes. Indomethacin has the ability to displace, in a dose-dependent manner, ANS (1-anilino-8-naphthalene sulphonate), a fluorescent anionic probe previously bound to the head group of phosphatidylcholine molecules. Estimations of the resonance fluorescence transfer between naproxen and the surface probe ANS or the hydrophobic probe, pyrene, bound to dipalmitoylphosphatidylcholine (DPPC) vesicles revealed that naproxen diffuses within the phospholipid bilayers. The dynamic of the gastric lipid material extracted from the surface scraping material (SSM) of the mucosa was altered by the NSAID as shown by the increase in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) (at 25 degrees, rSSM = 0.106+/-0.006, rssM + indomethacin = 0.137+/-0.005, and rSSM + naproxen = 0.133+/-0.007, P < 0.001). The thermodynamic behavior of a model bilayer containing DPPC was also perturbed by the NSAIDs tested. These results provide evidence that NSAIDs may reduce the ability of gastric surface-active phospholipids to form a hydrophobic protective layer.

Short report: treatment of gastric ulcer with lansoprazole or ranitidine: a multicentre clinical trial.

We studied the effectiveness of lansoprazole and ranitidine in promoting gastric ulcer healing in a multicentre double-blind trial, by comparing the proportion of healed ulcers after 4 and 8 weeks of treatment. One hundred and fifty-eight patients were randomly given either ranitidine (150 mg each morning and at bedtime) or lansoprazole (30 mg each morning and placebo at bedtime). One hundred and twenty-eight patients completed the trial (62 taking lansoprazole, 66 taking ranitidine). Fifty-one (80%) of those treated with lansoprazole and forty-two (62%) of those treated with ranitidine had healed ulcers at 4 weeks (P < 0.05). Sixty-one (98%) patients who received lansoprazole and 57 (86%) who received ranitidine had healed ulcers at 8 weeks (P < 0.05). The observed differences were not significant in the intention-to-treat analysis. No serious adverse event was reported with lansoprazole.

Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study.

BACKGROUND: Prokinetic agents have shown variable efficacy in the treatment of functional dyspepsia. Mosapride is a new prokinetic 5-hydroxytryptamine-4 agonistic agent. AIM: To evaluate the efficacy of three dosage regimens of mosapride compared with placebo in the treatment of functional dyspepsia. METHODS: Patients were randomly allocated to treatment with placebo or mosapride (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double-blind, prospective, multicentre, multinational study. The change in symptom severity score from an untreated baseline week to the sixth week of treatment was used to compare treatment efficacy. RESULTS: There were 141, 140, 143 and 142 patients valid for evaluation in the intention-to-treat population in the placebo, mosapride 5 mg b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The mean changes in the overall dyspeptic symptom score were - 0.90, - 0.94, - 0.88 and - 0.89, respectively, and the proportions of patients feeling better at the end of the treatment period were 60%, 59%, 59% and 61%, respectively. No statistically significant difference was seen. CONCLUSIONS: Treatment of functional dyspepsia with mosapride was not superior to placebo. The result raises the question of whether treatment with prokinetic agents is appropriate for functional dyspepsia.