C. Calabrese

Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment.

BACKGROUND:Dilation of intercellular spaces (DIS) of human esophageal epithelium, evident at transmission electron microscopy (TEM), is an early marker of damage caused by gastroesophageal reflux, but its reversibility after therapy has not been investigated.AIM:To evaluate whether omeprazole can induce the healing of DIS.METHODS:Thirty-eight symptomatic patients, 22 with nonerosive reflux disease (NERD) and 16 with erosive esophagitis (EE), classified on the basis of 24-h pH monitoring, were enrolled. During upper gastrointestinal endoscopy, six biopsies from apparently normal mucosa were taken within the lower 5 cm of the esophagus for histological and TEM analysis. One hundred computer measurements were taken on TEM photomicrographs of the specimens in each patient. After 3 months of omeprazole 40 mg/die a further endoscopy with biopsies was performed. In patients with persistent heartburn and/or incomplete ultrastructural recovery of esophageal epithelium, a new endoscopy was performed after 3 more months of treatment.RESULTS:After 3 months of therapy, 35 patients (92.1%) showed a complete recovery of DIS and resolution of heartburn. Three patients required 3 more months of therapy because of an incomplete recovery of the epithelium correlated with sporadic heartburn. Healing of the mucosa was achieved in two patients, whereas one had an incomplete recovery of DIS with persistent heartburn.CONCLUSIONS:Three and six months of omeprazole therapy led to a complete recovery of DIS in 92.1% and 97.4% of cases, respectively. No significant differences of DIS between NERD and EE were noted. Complete recovery of DIS was accompanied by regression of heartburn in all cases.

High-Dose Probiotics for the Treatment of Active Pouchitis

PurposePouchitis is the major long-term complication after ileal-pouch anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment in this condition. Recently, we have shown the efficacy of a highly concentrated probiotic preparation (VSL#3, 900 billions/sachet lyophilized viable bacteria) in preventing relapses of chronic pouchitis and in preventing pouchitis onset. This study was designed to evaluate the efficacy of high-dose VSL#3 in the treatment of mildly active pouchitis.MethodsTwenty-three consecutive patients with mild pouchitis, defined as a score of between 7 and 12 in the Pouchitis Disease Activity Index, which includes clinical, endoscopic, and histological criteria, were treated with VSL#3, 2 sachets b.i.d. (3600 billion bacteria/day) for four weeks. Symptomatic, endoscopic, and histologic evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of ≤2, endoscopic score of ≤1, and total Pouchitis Disease Activity Index score of ≤4. Patients in remission after treatment were treated with VSL#3, 1 sachet b.i.d. (1800 billion bacteria), as maintenance treatment for six months. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire.ResultsSixteen of 23 patients (69 percent) were in remission after treatment. The median total Pouchitis Disease Activity Index scores before and after therapy were 10 (range, 9–12) and 4 (range, 2–11), respectively (P < 0.01). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 110 (range, 90–140) to 200 (range, 95–220; P < 0.001). All 16 patients who went into remission maintained remission during maintenance treatment. Only one patient experienced a transient bloating at the beginning of treatment.ConclusionsHigh doses of the probiotic VSL#3 are effective in the treatment of mild pouchitis. Further controlled studies are warranted.

Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux.

Background : The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid.

Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis

BACKGROUND The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pughs score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high α fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline α fetoprotein levels ⩾20 ng/ml. CONCLUSIONS Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.

Oral budesonide in the treatment of chronic refractory pouchitis

Background  Pouchitis is the major long‐term complication after ileal‐pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory.

Short‐term treatment with infliximab in chronic refractory pouchitis and ileitis

Background  Chronic refractory pouchitis is a long‐term complication after ileal pouch‐anal anastomosis and it may be associated with ileal inflammation.

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.

Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia

Background—The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. Aims—To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. Patients and controls—Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p<0.001). Methods—Immunohistochemistry was performed on 3 μm sections of rectal biopsy specimens incubated with 5′-bromodeoxyuridine. Results—The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (φh value) was significantly higher in patients with CAG or ZES compared with controls (p<0.01 in both patient groups versus controls). Conclusions—Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Urease-Positive Bacteria Other than Helicobacter pylori in Human Gastric Juice and Mucosa

BACKGROUND AND AIM:Many bacteria carry the urease enzyme in different human ecosystems, but Helicobacter pylori is the only known bacterium showing urease activity in gastric ecosystems. For this reason, the rapid urease test (RUT) on gastric biopsies and urea breath test (C-UBT) are used to detect H. pylori infection.The aim of this study was to evaluate the presence of urease-positive bacteria other than H. pylori in gastric juice and mucosa in hypochlorhydric subjects.METHODS:Twenty-five hypochlorhydric and 10 normochlorhydric patients were analyzed for the presence of H. pylori and bacterial overgrowth both in gastric juice and on the mucosa. During upper gastrointestinal endoscopy at 8.00 a.m. gastric juice samples and biopsy specimens were taken from the antrum and corpus. All samples were analyzed using standard microbiological procedures like aerobic/anaerobic growth, gram-staining, gas chromatography, API test, 96-clone method, and selective medium to search for specific bacteria. In addition, all strains isolated were screened for urease activity using the CP-test. Urease positive strains were tested for the capacity to survive in an acid environment with or without urea (10 mM/L), at pH 7, 4, 3, and 2, respectively, at different times (0, 20, 30, and 60 min).RESULTS:Six hypochlorhydric patients had 10 strains of urease-positive non-H. pylori bacteria among which Staphylococcus capitis urealiticum showed the strongest urease activity.CONCLUSIONS:Hypochlorhydric patients present many urease-positive bacteria other than H. pylori. The strong urease activity may be responsible for false positive results at RUT or UBT test in patients with suspected H. pylori infection.

Fungal dysbiosis in mucosa-associated microbiota of Crohn’s disease patients

BACKGROUND AND AIMS Gut microbiota is involved in many physiological functions and its imbalance is associated with several diseases, particularly with inflammatory bowel diseases. Mucosa-associated microbiota could have a key role in induction of host immunity and in inflammatory process. Although the role of fungi has been suggested in inflammatory disease pathogenesis, the fungal microbiota has not yet been deeply explored. Here we analysed the bacterial and fungal composition of the mucosa-associated microbiota of Crohns disease patients and healthy subjects. METHODS Our prospective, observational study evaluated bacterial and fungal composition of mucosa-associated microbiota of 23 Crohns disease patients [16 in flare, 7 in remission] and 10 healthy subjects, using 16S [MiSeq] and ITS2 [pyrosequencing] sequencing, respectively. Global fungal load was assessed by real time quantitative polymerase chain reaction. RESULTS Bacterial microbiota in Crohns disease patients was characterised by a restriction in biodiversity. with an increase of Proteobacteria and Fusobacteria. Global fungus load was significantly increased in Crohns disease flare compared with healthy subjects [p < 0.05]. In both groups, the colonic mucosa-associated fungal microbiota was dominated by Basidiomycota and Ascomycota phyla. Cystofilobasidiaceae family and Candida glabrata species were overrepresented in Crohns disease. Saccharomyces cerevisiae and Filobasidium uniguttulatum species were associated with non-inflamed mucosa, whereas Xylariales order was associated with inflamed mucosa. CONCLUSIONS Our study confirms the alteration of the bacterial microbiota and is the first demonstration of the existence of an altered fungal microbiota in Crohns disease patients, suggesting that fungi may play a role in pathogenesis.