Mesalazine with or without cholestyramine in the treatment of microscopic colitis: Randomized controlled trial

Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10–15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed. Methods and Results: A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology. Conclusions: Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC

Erosions or not in GERD? The potential role of esophageal cell kinetics

Gastro-oesophageal reflux is an almost universal daily occurrence, but only a small percentage of the population develops gastro-oesophageal reflux disease (GORD) and, among them, a small number develop erosive oesophagitis (ERD) or one of its complications. It is well accepted that the pathophysiology of GORD is related to failure of antireflux mechanisms but several phenomena are not fully explained on the basis of this sequence. There is no apparent relation between damage and the amount and quality of refluxate. It is not known why the same amount of refluxate determines GORD in one patient and not in another.2 It is also unclear whether there is a relation between these unexplained questions and the possible influence of proliferative responses of epithelial proliferating cells to damage. Hence we evaluated cell proliferation of the oesophageal epithelium using Ki67 immunostaining in normal subjects and in patients with GORD, with or without erosions. Thirty five subjects were enrolled: nine were healthy voluntary controls with normal pH testing and normal endoscopic, histological, and ultrastructural patterns. Twenty six patients were affected by GORD, defined as frequent heartburn for at least a year, and abnormal 24 hour pH, histological, and ultrastructural parameters. Of these 26 patients, 13 had a normal appearing oesophageal mucosa at endoscopy (NERD) while 13 had ERD. All subjects underwent gastroscopy; six biopsies were obtained within the lower 5 cm of the oesophagus from areas of macroscopically intact oesophageal mucosa. The presence of oesophagitis was graded according to the Los Angeles classification. pH parameters were not statistically different between NERD and ERD. At transmission electron microscopy (TEM), all patients with GORD, with or without erosions, showed ultrastructural signs of damage, defined by the presence of dilation of intercellular spaces (>0.74 \ub5m). No significant differences were observed between the two groups. For assessment of the proliferative activity of epithelial cells, we used the immunohistochemical approach based on the Ki67 marker of cell proliferation which provides an accurate estimate of the cell growth fraction. Ki67-labelling index (LI) ranged from 8.9% to 74.4% among all patients (mean (SD) 33.5 (19.7)%; median 27.8%). Mean Ki67-LI values for the three groups of patients (normal, NERD, and ERD) were 62.2%, 29.8%, and 17.2%, respectively, and the difference among the groups was significant (p<0.01). This study was carried out on biopsies taken only in normal appearing mucosa at endoscopy. In this way we studied the behaviour of the mucosa exposed to chronic acid insult but far from erosions, and in particular from reparative changes secondary to lack of superficial mucosa where basal cell hyperplasia and elongation of papillae have been reported.8 We found that in all patients, oesophageal epithelium exposed to chronic acid exposure in normal appearing mucosa had a proliferation rate inferior to that of normal subjects: GORD patients had cell kinetics that were reduced to 50% and 25% in NERD and ERD patients, respectively. In order to explain the reduced proliferation rate observed in GORD patients, two different pathogenetic mechanisms can be suggested. Cell proliferation changes could be a consequence of either chronic cell damage or an intrinsic reduced ability of cells to proliferate, the one mechanism not excluding the other. Regarding the first hypothesis, little is known of the behaviour of the oesophageal mucosa stressed by chronic acid and pepsin insult. The second pathogenetic hypothesis concerns the existence of an individual predisposition to stronger or weaker cell proliferative efficacy of epithelial mucosa to chronic insults. This concept supports the idea that in genetically susceptible individuals, chronic acid and pepsin exposure may trigger or accelerate the development of ERD while in others more efficient cell proliferative activity can repa..

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%, P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases

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Superoxide dismutase in gastric adenocarcinoma: is it a clinical biomarker in the development of cancer?

Gastric cancer is the second most common cancer worldwide. The involvement of reactive oxygen species (ROS) in the pathogenesis of gastric malignancies is well known. Many human tumours have shown significant changes in the activity and expression of superoxide dismutase (SOD), which might be correlated with clinical-pathological parameters for the prognosis of human carcinoma. The aim of this study is the detection of MnSOD and CuZnSOD activity and their expression in gastric adenocarcinoma and healthy tissues. Gastric samples (adenocarcinoma and healthy tissues) harvested during endoscopy or resected during surgery were used to determine MnSOD and CuZnSOD activity and expression by spectrophotometric and Western blotting assays. The total SOD activity was significantly higher (p&lt;0.05) in healthy mucosa with respect to gastric adenocarcinomas. No differences were found in MnSOD activity and, on the contrary, CuZnSOD activity was significantly lower (p&lt;0.001) in cancer samples with respect to normal mucosa. The rate of MnSOD/CuZnSOD activity in adenocarcinoma was over ninefold higher than that registered in healthy tissues (p&lt;0.05). Moreover, in adenocarcinoma MnSOD activity represented the 83% of total SOD with respect to healthy tissues where the ratio was 52% (p&lt;0.001). On the contrary, in cancer tissues, CuZnSOD activity accounted for only 17% of the total SOD (p&lt;0.001 if compared with the values recorded in normal mucosa). After immunoblotting, MnSOD was more expressed in adenocarcinoma with respect to normal mucosa (p&lt;0.001), while CuZnSOD was similarly expressed in adenocarcinoma and healthy tissues. The SOD activity assay might provide a specific and sensitive method of analysis that allows the differentiation of healthy tissue from tumour tissue. The MnSOD to CuZnSOD activity ratio, and the ratio between these two isoforms and total SOD, presented in this preliminary study might be considered in the identification of cancerous from healthy control tissue