[Large iatrogenic colonic perforation treated by endoscopic suturing]. / Large perforation colique au cours d'une coloscopie traitée par fermeture endoscopique: rapport de deux observations.

Perforation of the colon during colonoscopy is still one of the most severe complications of this technique and occurs with a frequency of between 0.12 % and 0.2 % of cases after diagnostic colonoscopy and in up to 3 % of patients after therapeutic colonoscopy. The site of perforation is usually the sigmoid colon. The gold standard for treatment of this complication is surgery to be performed as rapidly as possible: a simple suture and peritoneal cleaning, with limited resection and anastomosis or colostomy only in case of confirmed fecal peritonitis. However, interventional endoscopy has made progress, in particular endoscopic suturing and Natural Orifice Transluminal Endocopic Surgery (NOTES) has been developed. There are several reports of endoscopically sutured perforated colons, most less than 10mm. We report our experience of two colonic perforations which were at least 10mm treated by endoscopic suturing with hemoclips: a perforated sigmoid diverticulum during simple colonoscopy in the first case and a large polypectomy by endoscopic mucosal resection of the ascending colon in the second.

Low risk of irritable bowel syndrome after Clostridium difficile infection.

OBJECTIVE: The incidence of postinfectious irritable bowel syndrome (IBS) ranges between 4% and 32% of individuals after bacterial or parasitic infection. This study analyzed IBS symptoms in hospitalized patients three months after a symptomatic Clostridium difficile infection. PATIENTS AND METHODS: All patients with a proven, symptomatic C difficile infection identified in the department of bacteriology over a four-month period were considered for enrolment. Patients were excluded in cases of pre-existing IBS or other organic gastrointestinal diseases. Patients completed both modified Talley and Rome II questionnaires within five days of clinical improvement with metronidazole and at three months postinfection, when stools were cultured and C difficile toxins were examined to exclude ongoing infection. RESULTS: Twenty-three patients were evaluated three months after infection with C difficile. Just after infection, 15 patients were symptom free, whereas eight patients exhibited symptoms suggestive of IBS. Three months after infection, 22 patients remained symptom free, whereas one patient presented with symptoms indicative of IBS. That female patient had a prolonged infection without vomiting. CONCLUSIONS: We have shown that while transient functional bowel disorder occurred in 34.7% of patients (eight of 23 patients) recently infected with C difficile, only 4.3% of patients (one of 23 patients) had symptoms indicative of IBS after three months (ie, postinfectious IBS). Because an age-related reduction in immune responsiveness has been documented, it can be speculated that the low incidence of postinfectious IBS may be explained by the older age of the study population. Therefore, it cannot be excluded that the findings may be different in younger patients.

Review article: yeast as probiotics -- Saccharomyces boulardii.

BACKGROUND: Probiotics are defined as live micro-organisms which confer a health benefit on the host. Although most probiotics are bacteria, one strain of yeast, Saccharomyces boulardii, has been found to be an effective probiotic in double-blind clinical studies. AIMS: To compare the main properties that differentiates yeast from bacteria and to review the properties of S. boulardii explaining its potential benefits as a probiotic. METHODS: The PubMed and Medline databases were searched using the keywords 'probiotics', 'yeast', 'antibiotic associated diarrhea', 'Saccharomyces boulardii','bacterial diarrhea' and 'inflammatory bowel disease' in various combinations. RESULTS: Several clinical studies have been conducted with S. boulardii in the treatment and prevention of various forms of diarrhoea. Promising research perspectives have been opened in terms of maintenance treatment of inflammatory bowel diseases. The mechanism of S. boulardii's action has been partially elucidated. CONCLUSION: Saccharomyces boulardii is a strain of yeast which has been extensively studied for its probiotic effects. The clinical activity of S. boulardii is especially relevant to antibiotic-associated diarrhoea and recurrent Clostridium difficile intestinal infections. Experimental studies clearly demonstrate that S. boulardii has specific probiotic properties, and recent data has opened the door for new therapeutic uses of this yeast as an 'immunobiotic'.

[Cholangiography by magnetic resonance for detection of cholelithiasis: comparison with endoscopic retrograde cholangiography, operative cholangiography and percutaneous cholangiography]. / Colangiografía por resonancia magnética para la detección de litiasis de la via biliar principal: comparación con la colangiografía retrógrada endoscópica, Colangiografía per operatoria y colangiografía percutánea.

UNLABELLED: To evaluate the diagnostic efficiency of the magnetic resonance cholangiography (MRC) in the detection of main bile duct stones in a set of 102 patients. METHODOLOGY: Criteria of inclusion were: Clinic and biological suspicion of biliary stones obstruction with exams of first intention no contributive. We used the "turbo spin echo" sequences with thick slices in single shot mode and fine slides with reconstruction in 3D by a computer. Exams of reference were the endoscopic retrograde cholangiography (76.47%), an intraoperative cholangiography (20.59%) and a per-cutaneous cholangiography (2.94%). RESULTS: Stones of the main bile duct have been diagnosed at thirty-five patient (35.7%); we had 3 positive forgeries and 6 negative forgeries of the MRC. The sensitivity was 82,9%, the specificity of 95,5%, the positive predictive value and the negative predictive value were, respectively, of 90,6% and 91,4%. The observant variance test was excellent (kappa = 0.83). Mistakes of diagnosis of the MRC were bound to: stones less than 3 mms with a bile duct no dilated, malignant stenosis, structural details as the presence of a duodenal diverticula's or severe duodenitis and a certain difficulty to see the sphincter complex. CONCLUSION: Performances of the CIRM was good, and only in very particular cases, it was the origin of confusions.

Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study.

BACKGROUND AND AIMS: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. METHODS: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0-10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. RESULTS: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p<0.01), day 30 (54.5 (37.6); p<0.01), and day 60 (60.8 (37.3); p<0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. CONCLUSIONS: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases.

[Retained fecalith after laparoscopic appendicectomy]. / Coprolithe résiduel, après appendicectomie coelioscopique.

The subhepatic abscess due to retained fecalith is a rare complication following appendicectomy. The incidence of this complication is probably going to increase due to high rate of laparoscopic appendicectomy. We report 2 cases of subhepatic abscess 1 and 2 years after laparoscopic appendectomies. This potentially serious complication could be preventing with technical recommendations. When it occurs, this complication has to be directly treated by surgical drainage, percutaneous drainage couldn't be successful because it leaves fecalith in its place which is a cause of recurrence. Our reports are the first to use a laparoscopic treatment of this complication.

Gastrointestinal tolerability of ibuprofen compared with paracetamol and aspirin at over-the-counter doses.

This multicentre, randomized, investigator-blinded, parallel-group study compared the gastrointestinal (GI) tolerability of ibuprofen, paracetamol and aspirin at over-the-counter doses for common pain indications. Patients (of whom 8633 were evaluable) took either ibuprofen up to 1200 mg daily, or paracetamol or aspirin, each up to 3000 mg daily, for 1-7 days. The main outcome was the proportion of patients with GI adverse events. There were significantly more patients who suffered GI adverse events, principally abdominal pain, dyspepsia, nausea and diarrhoea, with aspirin (18.5%) than with ibuprofen (11.5%), but the difference between ibuprofen and paracetamol (13.1%) was not significant. Significantly more of those patients with a history of non-ulcer GI disease (n = 371) developed GI adverse events than did those with no such history; the incidence of GI adverse events in both groups was lowest with ibuprofen. More women than men experienced GI adverse events (15.5% versus 12.8%). The higher incidence of GI adverse events with aspirin was evident from the first day of treatment. In conclusion, the GI tolerability of ibuprofen, at over-the-counter doses of up to 1200 mg daily for up to 7 days, was at least as good as that of paracetamol and significantly better than that of aspirin.

Fatigue is associated with high circulating leptin levels in chronic hepatitis C.

BACKGROUND AND AIMS: Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor alpha (TNF-alpha). METHODS: Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-alpha. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients. RESULTS: Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) v 17.7 (16.9); p<0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) v 6.4 (4.1) ng/ml; p<0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (r=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (r=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients. CONCLUSIONS: Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.

Decreasing oesophageal acid exposure in patients with GERD: a comparison of rabeprazole and omeprazole.

BACKGROUND: Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD). AIM: This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD. METHODS: Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period. RESULTS: At the end of study, the percentage time (mean +/- s.d.) with pH < 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 +/- 4.77; 2.53 +/- 4.27; 2.02 +/- 1.71 and 2.91 +/- 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated. CONCLUSIONS: Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.

Outcome of patients treated with home enteral nutrition.

BACKGROUND: The aims of this study were to prospectively analyze the 1-month mortality and long-term outcome of home enteral nutrition (HEN) patients in order to determine the benefits of this treatment. METHODS: Between 1990 and 1996, 417 patients, aged 64 +/- 25 years, were discharged on HEN and followed up until December 31, 1998, when outcome was assessed, which allowed us to determine survival probabilities and conditions associated with survival. RESULTS: The mean duration of HEN was 242 +/- 494 days, with a 24- to 103-month follow-up. Probabilities of being alive at 1 month, 1 year, and 5 years were 80%, 41.7%, and 25%, respectively. Factors associated with death were dementia, neurologic disease, head and neck cancer, AIDS, and age over 70 years. A total of 5.5% of patients remained dependent on HEN, 32.6% resumed full oral nutrition, 20.2% of patients died during the first month on HEN, and 35% died after more than 1 month on HEN (219 +/- 257 days). A total of 6.7% of patients stopped HEN for other reasons. CONCLUSIONS: HEN provides well-tolerated long-term nutritional support in many patients. However, because of their likelihood of being old and the nature of the underlying disease, these patients as a group tend to have a modest prognosis. This calls for the determination of more accurate selection criteria, and the measurement of the impact of HEN on quality of life.

[Atrophic polychondritis associated with ulcerative colitis]. / Polychondrite chronique atrophiante associée à une rectocolite hémorragique.

We report the case of a 46-year-old patient in whom ulcerative colitis had been diagnosed three years ago. He was admitted to the hospital for swelling of the nose. Clinical course and complementary exams led us to diagnose atrophic polychondritis. Twelve cases of such an association have been published so far.

Antiproliferative effects of nitrosulindac on human colon adenocarcinoma cell lines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colon cancer, but their use is limited by toxicity in the gastrointestinal tract. The coupling of a nitric oxide-releasing moiety to NSAIDs strongly reduces these side effects. We demonstrated that the NO-releasing sulindac (nitrosulindac) has much more potent effects on colon adenocarcinoma cell lines compared to sulindac. Moreover, it could inhibit the growth of cells in soft agar experiments, demonstrating the antineoplastic activity at low concentration of nitrosulindac. However, this reduction in the growth of colon cancer cells seemed to be independent of the classical apoptosis pathway and could be explained by a cytostatic effect. Nitrosulindac caused a light perturbation of the cell cycle parameters not linked to a modification of the levels of p21 or the proliferating cell nuclear antigen. Moreover, neither sulindac, nor nitrosulindac, were able to inhibit the NF-kappa B pathway. These data suggested that nitrosulindac could be a better solution compared to other NSAIDs in the treatment of colon cancer.

Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation: epidemiological study in an unselected population.

Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of cholesterol. The aim of this study was to assess in an unselected population whether these hypolipidemic drugs are risk factors for cholelithiasis or, conversely, are protective agents. Both sexes, all socioeconomic categories, pregnant women, and cholecystectomized subjects were included. Clinical data collection and gallbladder ultrasonography were both carried out in a double-blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA reductase inhibitors were simvastatin and pravastatin. On univariate analysis, age (>50 years), sex, and use of fibrates were found to be significantly related to the presence of cholelithiasis. Age, sex, and fibrate treatment remained independently correlated with the presence of gallstones on multivariate analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The HMG-CoA reductase inhibitors were not associated with a protective effect on univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were found to increase the risk of gallstone formation.

Argon plasma endoscopic section of biliary metallic prostheses.

We report our recent experience of using argon plasma to endoscopically cut biliary Wallstent prostheses in these patients. The first patient had a bleeding duodenal ulceration caused by the impaction of the prosthesis meshes whereas the second patient had an ill-positioned biliary stent with impaction into the opposite duodenal wall. Both prostheses were shortened using argon plasma. In the third patient, the lower extremity of a obstructed biliary Wallstent was positioned in the third duodenum preventing its endoscopic catheterization. After shortening using argon plasma, a new plastic stent could be inserted to allow drainage. The outcomes in these cases demonstrate the feasibility of endoscopically shortening metallic Wallstents after release using argon plasma.

Implication of mitogen-activated protein kinases in T84 cell responses to enteropathogenic Escherichia coli infection.

Enteropathogenic Escherichia coli (EPEC) infection of T84 cells induces a decrease in transepithelial resistance, the formation of attaching and effacing (A/E) lesions, and cytokine production. The purpose of this study was to investigate the ability of EPEC to activate mitogen-activated protein (MAP) kinases in T84 cells and to correlate these signaling pathways with EPEC-induced cell responses. T84 cells were infected with either the wild-type (WT) EPEC strain E2348/69 or two mutants, intimin deletion strain CVD206 (deltaeaeA) and type III secretion apparatus mutant strain CVD452 (deltaescN::aphA). Infection of T84 cells with WT but not mutant EPEC strains induced tyrosine phosphorylation of several proteins in T84 cells, including the p46 and p52 Shc isoforms. Kinetics studies revealed that ERK1/2, p38, and c-Jun N-terminal kinase (JNK) MAP kinases were activated in cells infected with strain E2348/69 but not with the mutant strains. Inhibition of MAP kinases with PD98059 or SB203580 did not affect the EPEC-induced decrease in transepithelial resistance or actin accumulation beneath the WT bacteria, but these two inhibitors significantly decreased interleukin-8 (IL-8) synthesis. We demonstrate that EPEC induces activation of ERK1/2, p38, and JNK cascades, which all depend on bacterial adhesion and expression of the bacterial type III secretion system. ERK1/2 and p38 MAP kinases were equally implicated in IL-8 expression but did not participate in A/E lesion formation or transepithelial resistance modification, indicating that the signaling pathways involved in these events are distinct.

Acarbose and lymphocytic colitis.

We report a case of lymphocytic colitis induced by acarbose. Our immunopathological findings shown before and after rechallenge are consistent with a colonic immune-cell activation by the drug.

Resting energy expenditure in chronic hepatitis C.

BACKGROUND/AIMS: Hypermetabolism is considered to be of clinical interest in liver disease and in several chronic viral infections. Whether resting energy expenditure (REE) increases during chronic hepatitis C is not known. Our aims were: (a) to determine the metabolic state of patients with chronic hepatitis C, and (b) to evaluate the effects of interferon therapy on REE. METHODS: Forty-seven patients and 20 controls were studied. Sixteen patients failed to respond to interferon and 12 patients stopped the treatment during the first 2 months for various reasons. The 19 responders all received 1 year of interferon. REE (indirect calorimetry) and fat-free mass (FFM, bioelectric impedance analysis) were evaluated before (day 0) and after 90, 180, and 360 days of interferon. The virus load was evaluated in patients before treatment. RESULTS: On day 0, REE expressed as a ratio of FFM (REE/FFM) was higher in patients than in controls (129.2 +/- 14.7 vs 117.9 +/- 9.6 kJ kg FFM(-1) 24 h(-1), p<0.01), and was positively correlated with the viral load (r=0.45, p=0.01). On day 90, REE/FFM had significantly decreased in responders but it did not decrease in non-responders (p<0.01). In responders, REE/FFM on days 180 and 360 was similar to that of the controls. CONCLUSIONS: Chronic hepatitis C induces hypermetabolism that is normalized by interferon therapy in responders. The underlying mechanisms of chronic hepatitis C-induced hypermetabolism and its clinical relevance remain to be determined.

Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells.

Use of the nonpathogenic yeast Saccharomyces boulardii in the treatment of infectious diarrhea has attracted growing interest. The present study designed to investigate the effect of this yeast on enteropathogenic Escherichia coli (EPEC)-associated disease demonstrates that S. boulardii abrogated the alterations induced by an EPEC strain on transepithelial resistance, [(3)H]inulin flux, and ZO-1 distribution in T84 cells. Moreover, EPEC-mediated apoptosis of epithelial cells was delayed in the presence of S. boulardii. The yeast did not modify the number of adherent bacteria but lowered by 50% the number of intracellular bacteria. Infection by EPEC induced tyrosine phosphorylation of several proteins in T84 cells, including p46 and p52 SHC isoforms, that was attenuated in the presence of S. boulardii. Similarly, EPEC-induced activation of the ERK1/2 mitogen-activated protein (MAP) kinase pathway was diminished in the presence of the yeast. Interestingly, inhibition of the ERK1/2 pathway with the specific inhibitor PD 98059 decreased EPEC internalization, suggesting that modulation of the ERK1/2 MAP pathway might account for the lowering of the number of intracellular bacteria observed in the presence of S. boulardii. Altogether, this study demonstrated that S. boulardii exerts a protective effect on epithelial cells after EPEC adhesion by modulating the signaling pathway induced by bacterial infection.

Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.

OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that includes bacterial chitinases. The pattern of its expression in certain tissues such as human liver or cartilage suggests a function in remodelling or degradation of extracellular matrix. The purpose of this study was to assess whether circulating YKL-40 might be a serum fibrosis marker in alcoholics. METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men, 40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum fibrosis markers such as hyaluronate were also measured. Fibrosis and inflammation in liver biopsy were evaluated using a semi-quantitative scoring system. RESULTS: Plasma YKL-40 increased in parallel with the severity of fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic inflammation (P<0.01). Receiver operating characteristic curves of Chondrex revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however, the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis displayed a Chondrex plasma level above this threshold. A positive correlation was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative correlation was shown between Chondrex and the prothrombin index (r=-0.37, P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use of Chondrex in a screening programme. High levels of Chondrex (above 330 microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may reflect the remodelling of liver fibrosis in alcoholics.