C. Tosti

IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis.

Helicobacter pylori (Hp) infection is associated with gastric inflammation and ulceration. The pathways of tissue damage in Hp-infected subjects are complex, but evidence indicates that T cell-derived cytokines enhance the synthesis of matrix metalloproteinases (MMP) that contribute to mucosal ulceration and epithelial damage. In this study, we have examined the role of the T cell cytokine IL-21 in Hp-infected gastric mucosa and evaluated whether IL-21 regulates MMP production by gastric epithelial cells. We show that IL-21 is constitutively expressed in gastric mucosa and is more abundant in biopsy specimens and purified mucosal CD3+ T cells from Hp-infected patients compared with normal patients and disease controls. We also demonstrate that IL-21R is expressed by primary gastric epithelial cells, as well as by the gastric epithelial cell lines AGS and MKN28. Consistently, AGS cells respond to IL-21 by increasing production of MMP-2 and MMP-9, but not MMP-1, MMP-3, MMP-7, or tissue inhibitors of MMP. Analysis of signaling pathways leading to MMP production reveals that IL-21 enhances NF-κB but not MAPK activation, and inhibition of NF-κB activation reduces IL-21-induced MMP-2 and MMP-9 production. Finally, we show that treatment of Hp-infected gastric explants with anti-IL-21 reduces epithelial cell-derived MMP-2 and MMP-9 production. These data indicate that IL-21 is overexpressed in Hp-infected gastric mucosa where it could contribute to increased epithelial gelatinase production.

Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability.

Background Sequential therapy (SQT) is effective in the eradication of Helicobacter pylori and could become an alternative to standard triple therapy (STT). Aim To compare the efficacy and tolerability of SQT, for either 8 or 10 days, with a 7-day STT. Methods A total of 270 naive H. pylori-positive patients were randomized to receive: SQT for 8 days (SQT-8, n=90) or 10 days (SQT-10, n=90) including esomeprazole 20 mg twice daily (bid) associated with amoxicillin 1000 mg bid (early 4 and 5 d, respectively), followed by esomeprazole 20 mg bid associated with clarithromycin 500 mg bid plus tinidazole 500 mg bid (last 4 and 5 d, respectively); STT (n=90) including esomeprazole 20 mg bid plus amoxicillin 1000 mg bid and clarithromycin 500 mg bid for 7 days. Tolerability was assessed by scoring the severity of symptoms. Results Eradication rates after SQT-8 and SQT-10 were higher than that of after STT at both intention-to-treat (83% and 86% vs. 66%, P<0.02) and per-protocol analysis (90% and 88% vs. 75%, P<0.05), whereas no difference was found between the 2 SQTs. Conclusions This study shows that SQT, for 8 or 10 days, is well tolerated and highly effective in H. pylori eradication and could represent a valid alternative to STT. Further studies, with more power, on larger populations and from other countries are necessary to validate the present findings.

Rofecoxib and early relapse of inflammatory bowel disease: an open-label trial

Background : The safety and efficacy of selective cyclo‐oxygenase‐2 inhibitors in inflammatory bowel disease are under investigation.

Unsedated transnasal versus transoral sedated upper gastrointestinal endoscopy: a one-series prospective study on safety and patient acceptability.

BACKGROUND While conventional oesophagogastroduodenoscopy is frequently performed under sedation to improve acceptability, transnasal oesophagogastroduodenoscopy would appear to be less invasive. STUDY AIMS To compare diagnostic accuracy, feasibility, acceptability and safety of transnasal oesophagogastroduodenoscopy without sedation versus conventional oesophagogastroduodenoscopy under sedation. PATIENTS Following anxiety assessment, 30 dyspeptic patients underwent transnasal oesophagogastroduodenoscopy under local anaesthesia (lidocaine) and conventional oesophagogastroduodenoscopy under conscious sedation (i.v. midazolam) on two consecutive days. Transnasal oesophagogastroduodenoscopy was performed with an ultrathin and conventional oesophagogastroduodenoscopy with a standard endoscope. METHODS Safety, evaluated by monitoring cardio-respiratory functions. Acceptability, rated according to discomfort and preference between the two examinations. Diagnostic accuracy evaluated taking into account endoscopic patterns and adequacy of biopsy specimens for histology. Feasibility, defined according to endoscopic performance, quality of images and overall opinion of the endoscopist. Only gastric biopsies were evaluated. RESULTS All patients but one who refused conventional oesophagogastroduodenoscopy underwent both transnasal oesophagogastroduodenoscopy and conventional oesophagogastroduodenoscopy. No cardiorespiratory complications occurred during either technique. Majority of patients (87%) preferred transnasal oesophagogastroduodenoscopy. Examinations were completed in all cases, with comparable endoscopic patterns. All biopsy specimens were suitable for histology. CONCLUSIONS Transnasal oesophagogastroduodenoscopy without sedation provides good diagnostic accuracy, is safer and better accepted than conventional oesophagogastroduodenoscopy under sedation and, therefore, represents a valid alternative in routine diagnosis of upper digestive tract diseases.

Maintenance treatment of Crohn's disease

The aetiology of Crohns disease is unknown and therefore no curative treatments are available for the disease. The natural history of Crohns disease is characterized by recurrent flare‐ups of symptoms. Several drug treatments are effective in inducing clinical remission. However, no drug treatments are available in order to prevent clinical relapses, although several drug regimens may delay clinical flare‐ups. Crohns disease treatment for maintaining clinical remission needs to be tailored in relation to specific characteristics of each patient. The frequency of clinical relapse indeed shows marked variations in subgroups of patients, as the likelyhood of relapse is higher in patients in clinical remission for less than 6 months. Treatment strategies for maintaining remission may therefore differ among inactive patients. In chronically active, steroid‐dependent or steroid‐refractory Crohns disease patients immunomodulatory drugs (azathioprine 2–2.5 mg/kg by mouth, 6‐mercaptopurine 1–1.5 mg/kg by mouth, or methotrexate 15–25 mg/i.m./week) should be added to oral mesalazine (2.4 g/day), while in long‐term inactive Crohns disease patients mesalazine alone may be effective in delaying relapse. Recently, treatment with anti‐tumour necrosis factor‐α monoclonal antibodies (Infliximab or CDP571) has shown efficacy in delaying relapse in responsive patients. One other issue which needs to be considered before selecting drug treatments for maintaining remission in Crohns disease, is that Crohns disease activity is currently assessed on the basis of standard clinical scores which may not appropriately reflect the biological activity of the disease. Clinical remission as defined by standardized scores may include heterogeneous subgroups of patients showing different endoscopic and histological activity or persistence of activated immunocompetent cells within the gut. Several sub‐clinical markers of relapse have indeed been reported in quiescent Crohns disease, although their usefulness in clinical practice in currently uncertain.

Bacteria and mucosal immunity

In normal individuals, the intestine is a site of intense immunological activity due to the continuous stimulation by luminal antigens mostly derived from the normal bacterial flora. This is reflected in the huge amount of IgA produced in the gut and the abundant T cells in the lamina propria and epithelium. It is also becoming clear that products of the normal flora may regulate the cytokine environment within the inductive sites of the mucosal immune responses, such as the Peyers patches of the small bowel. Thus normal flora could either negatively or positively regulate specific immune responses by dictating the profile of locally released cytokines. For example, it is known that in Crohns disease the antigens that drive the strongly polarized Th1 tissue-damaging response are derived from the normal bacteria flora. Emerging evidence also indicates that gut microflora can contribute to maintain the mucosal homeostasis by promoting the generation and/or expansion of counter-regulatory mechanisms.

Look out before polypectomy in patients with diverticular disease – a case of a large, inverted diverticulum of the colon resembling a pedunculated polyp

Diverticular disease of the colon may be responsible for abdominal symptoms requiring colonoscopy, which may reveal the presence of concomitant polyps. A polyp found during colonoscopy in patients with colonic diverticular disease may be removed by endoscopic polypectomy with electrosurgical snare, a procedure associated with an incidence of perforation of less than 0.05%. The risk of such a complication may be higher in the event of an inverted colonic diverticulum, which may be misinterpreted as a polypoid lesion at colonoscopy. To date, fewer than 20 cases of inverted colonic diverticula, diagnosed at colonoscopy or following air contrast barium enema, have been reported in the literature. The present report describes a 68-year-old woman who underwent a screening colonoscopy, which revealed a voluminous pedunculated polyp that was recognized to be an inverted giant colonic diverticulum before endoscopic polypectomy.

M1065 Sequential Regimens Have Greater Efficacy and Better Tolerability Than Standard Triple Therapy in the Eradication of Helicobacter pylori Infection

Background: Sequential therapy (SQT) has been reported to be effective in the eradication of Helicobacter pylori (HP) infection and, if more largely validated, could become a valid alternative to standard triple therapy (STT). Aim: To evaluate efficacy and tolerability of SQT, with two different durations, in comparison to a 7-day STT. Patients & Methods: A total of 270 naive HP+ patients were randomized to receive STT (n=90), including esomeprazole (ESO) 20 mg bid, plus amoxicillin (AMO) 1000 mg bid, and clarithromycin (CLA) 500 mg bid, for 7 days; SQT for 10 days (SQT-10, n=90), including ESO 20 mg bid, for 10 days, associated with AMO 1000 mg bid for early 5 days, followed by CLA 500 mg bid, plus tinidazole (TNZ) 500 mg bid, both in the last 5 days; SQT for 8 days (SQT-8, n=90), including ESO 20 mg bid, for 8 days, associated with AMO 1000 mg bid for early 4 days, followed by CLA 500 mg bid, plus TNZ 500 mg bid, both in the last 4 days. HP status was established by the agreement of two tests out of three chosen among urea breath test, stool antigen assay, urease rapid test and histology. Tolerability of regimens was assessed by scoring the severity of symptoms reported by patients in a predefined questionnaire. Results: Eradication rates achieved by SQT-10 and SQT-8 were significantly higher than that by STT at both intention-to-treat (86% and 83% vs. 66%, p<0.02) and per-protocol analysis (87% and 90% vs. 75%, p<0.01), while no difference was found among the two SQT therapies. Mean scores of symptoms occurring on SQT-8 were significantly lower than those on SQT10 (nausea: 2.83 ± 1.90 vs. 4.68 ± 4.00, p<0.01; taste perversion: 3.14 ± 1.96 vs. 9.42 ± 6.54, p<0.05) and STT (nausea: 2.83 ± 1.90 vs. 5.08 ± 4.70, p<0.01; diarrhea: 3.14 ± 1.96 vs. 4.11 ± 4.01, p<0.02). Conclusions: SQT for 10 or 8 days are more effective than STT for HP eradication. Among SQT the 8 days regimen appears to be better tolerated than 10 days regimen.

Local injection of infliximab in the postoperative recurrence of Crohn's Disease during endoscopy: A prospective longitudinal study

BACKGROUND Local injection of infliximab in Crohns disease (CD) lesions may reduce the risk of rare side effects, reduce the dose, and increase the efficacy of the drug. The objective was to prospectively assess the feasibility and the safety of local injection of infliximab for the postoperative recurrence of patients with CD who were followed for at least 1 year. METHODS In a pilot, open-label study, 8 patients with CD (3 men; median age 48 years, range 35-82 years) undergoing ileocolonoscopy were prospectively enrolled. Inclusion criteria included the following: (1) localized (<5 cm) recurrence, (2) inflammatory pattern, and (3) clinically inactive CD. At the first endoscopy, lesions were injected with infliximab (median, 30 mg; range, 8-60 mg); a control endoscopy was performed at 2 weeks in 4 patients (3 received a second injection followed by a control endoscopy at 6 weeks) and at 4 weeks in 4 patients (2 received a second injection followed by a control endoscopy at 8 weeks). OBSERVATIONS No patients showed side effects or clinical relapse in the short term and the long term (median follow-up, 20 months; range, 14-21 months). Endoscopic score improved in 3/8 patients. The histologic scores were reduced in 4 patients, worsened in 3, and were unchanged in one patient with CD. CONCLUSIONS Local injection of infliximab into patients with CD recurrence is feasible and safe, requiring a low dose. Present findings suggest the need of placebo-controlled trials to assess the efficacy of this new and safe procedure in subgroups of patients with CD.

Using the Video Endoscope Prototype Olympus XGIF-N160Y1 for Transnasal Gastroscopy: A Pilot Study of Feasibility and Tolerability

Using the Video Endoscope Prototype Olympus XGIF-N160Y1 for Transnasal Gastroscopy: A Pilot Study of Feasibility and Tolerability Italo Stroppa, Claudio Tosti, Cinzia Razzini, Sabrina Mazzocchi, Francesco Romeo, Francesco Pallone Background and Aim: The video endoscope Olympus XGif-N160Y1 (outer diameter:4.9 mm, total length:1410 mm, working length:1100 mm) is a prototype (PT) with only ‘‘up-down’’ movement, metallic distal tip and a deflexion capability of 210 up and 180 down. The aim of the study was to assess feasibility and tolerability of transnasal gastroscopy (TN) using this prototype. Methods: 50 consecutive patients eligible for TN were enrolled in the study (25 men, 25 female, age: 49 G 17 years). InIclusion criteria were: indication for gastroscopy, history of prior conventional gastroscopy and age O 14 years. All patient gave informed consent. Hamilton A scale was used to assess patients anxiety before endoscopy in all patients. A questionnaire was administered to all patient soon after TN examination was completed to explore patients satisfaction and preference for conscious sedation. Cardiorespiratory parameters (oxygen saturation, one-lead electrocardiogram) were recorded during endoscopy. Blood pressure was measured in different phases during the exam (baseline, esophagus, stomach, duodenum) and after exam. Cardiorespiratory parameters variations in each phase of the exam were compared by one way analysis of variance. Feasibility and image quality were evaluated by operator on a subjective scale. Results: Endoscopy was performed with a transnasal approach in every patient without complications. Procedure time was 5 G 3 minutes. All segment down to the second duodenal portion were visualized. In all patients biopsy samples were taken from both the antrum and the gastric body. Images quality was excellent in all examination as assessed by the subjective endoscopist’s evaluation. Anxiety was absent in 24 patients, mild in 15, moderate in 4 and need to treatment in 4. After satisfaction questionnaire was administered it appeared that none of the 24 patients with no anxiety and one of the 26 with any level of anxiety would have preferred conscious sedation. Only one patient reported pain at instrument insertion and during endoscopy. No significant changes in oxygen saturation and blood pressure occurred during the exam. Heart rate and rate-pressure product increased significantly during the endoscopy (p ! 0.01) and returned to baseline at the end of the exam. No ST-Tchanges or serious arhythmias occurred. Conclusions: Data of this pilot study show that unsedated transnasal gastroscopy by the prototype Olympus XGIF-N160Y1 is feasible and well tolerated by patients.