M. Lazzaroni

A comparison of two different doses of omeprazole versus ranitidine in treatment of duodenal ulcers

In a study involving three centers, 105 patients with duodenal ulcer proven by endoscopy were randomly assigned to treatment with either the H+, K+, ATPase inhibitor omeprazole (20 mg or 40 mg taken as a single morning dose), or ranitidine (150 mg morning and night). It was a double-blind study using a double-dummy technique. Clinical assessment and laboratory investigations were carried out at 2, 4, and 8 weeks; endoscopy was done at 2 weeks, and if not healed, at 4 and 8 weeks. The patients in the three treatment groups were well matched. Significantly more patients treated with omeprazole healed compared with ranitidine at 2 weeks (p = 0.007) and at 4 weeks (p = 0.007), but there was no statistically significant difference between the two omeprazole groups. Pain was of similar severity at the start in all groups, but patients treated with omeprazole had fewer days with pain (median values being omeprazole 20 mg: 2 days; omeprazole 40 mg: 1 day; ranitidine: 7 days). The difference between the combined omeprazole groups and ranitidine was significant (p less than 0.02). There was also a tendency towards less severe daytime pain on omeprazole during the first week. The difference was statistically significant between omeprazole (40 mg) and ranitidine for days 2-7 (p less than 0.01). No change in laboratory screen attributable to drug treatment occurred. After healing, 79 patients entered a 6-month follow-up study with endoscopy at 3 and 6 months or whenever symptoms occurred. After 6 months relapses occurred in 14/24, 19/23, and 15/25 after 20 mg omeprazole, 40 mg omeprazole, and ranitidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Eradication of Helicobacter pylori on Gastritis in Duodenal Ulcer Patients

The incidence and mean score of Helicobacter pylori-related, active antroduodenitis, lesions of superficial antral epithelium and duodenal gastric-type metaplasia were higher in endoscopic biopsies from a large series of patients with duodenal ulcer, when compared with asymptomatic patients or patients with non-ulcer dyspepsia. In 65 out of 73 patients with duodenal ulcer who could be followed up, H. pylori was eradicated using a combination of amoxycillin, 3 g daily, metronidazole, 1 g daily, and omeprazole, 20 mg daily. Rapid and permanent (6-month follow-up) abolition of both gastroduodenitis activity and lesions of the gastric surface epithelium was observed in these 65 patients. There was also a progressive decrease in total immune-inflammatory cells but without a substantial change in duodenal gastric-type metaplasia. Similar, but transient and quantitatively less prominent, improvements were observed in the antroduodenal mucosa, which had been temporarily cleared of H. pylori by treatment with omeprazole alone. Conversely, increased gastritis activity, epithelial lesions and immune-inflammatory cell scores were found in the short term in the corpus mucosa, which was not cleared of H. pylori after omeprazole treatment. It is concluded that, of the various H. pylori-related mucosal changes, antroduodenitis activity and antral epithelial lesions most closely reflect the severity of mucosal damage and are probably the most important factors in duodenal ulcerogenesis. Their complete and rapid suppression after bacterial eradication may be a key factor in preventing ulcer relapse.

Gastrointestinal side-effects of traditional non-steroidal anti-inflammatory drugs and new formulations.

Although adverse effects of non‐steroidal anti‐inflammatory drugs (NSAIDs) occur in only a small proportion of users, the widespread use of these drugs has resulted in a substantial overall number of affected persons who experience serious gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10–60% of NSAID users and lead to discontinuation of treatment in 5–15% of rheumatoid arthritis patients taking NSAIDs. It is now well established that the point prevalence of peptic ulcer disease in patients receiving conventional NSAID therapy ranges between 10 and 30%, representing a 10–30‐fold increase over that found in the general population. One of 175 users of conventional NSAIDs in the USA will be hospitalized each year for NSAID‐induced gastrointestinal damage. The mortality of hospitalized patients remains about 5–10%, with an expected annual death rate of 0.08%. The selective COX‐II inhibitors (rofecoxib, celecoxib, parecoxib, etoricoxib, valdecoxib, lumiracoxib) show consistently comparable efficacy to that of conventional non‐steroidal anti‐inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis and osteoarthritis, but have a significantly reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric effects of therapeutically active doses of COX‐II inhibitors are indistinguishable from placebo. The safety benefits of COX‐2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. These findings warrant the consideration of COX‐II inhibitors as first‐line therapy in patients requiring long‐term pain control.

Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study.

AIM To evaluate the efficacy of pantoprazole in preventing gastrointestinal lesions in patients with rheumatic diseases receiving continuous, long-term treatment with non-steroidal anti-inflammatory drugs. MATERIAL This was a prospective, randomised, double-blind, unbalanced, placebo-controlled, parallel group study. Outpatients (n= 104, age range 22-80 years, mean age 59.5) with rheumatoid arthritis or osteoarthritis, requiring chronic intake of NSAIDs (at least 8 weeks prior to the start of the study), were randomised and enrolled to receive either 40 mg pantoprazole (n=70) or placebo (n=34) once daily, for 12 weeks. Patients had endoscopically confirmed gastric and duodenal lesions grade 0, 1 or 2 (Lanza classification grade 0: normal to hyperaemic mucosa; grade 1: 1 to 3 erosions, submucosal haemorrhage or petechiae, grade 2: 4 to 10 erosions, submucosal haemorrhages or petechiae). Clinical and endoscopic evaluations were performed at baseline, after 4, and 12 weeks. The primary end-point of the study was the incidence of gastric or duodenal ulcers after 4 and 12 weeks of treatment. RESULTS Patients (n=95) were evaluated: 65 in the pantoprazole group and 30 in the placebo group. When considering all patients (those with Lanza score grade 0, 1, 2 at baseline), the overall proportion of patients in remission was 82% and 77% after 4 weeks, and 72% and 59% after 12 weeks in pantoprazole and placebo groups, respectively (cumulative survival analysis according to Kaplan-Meier). The difference between the treatment groups was even more marked when only those patients with normal mucosa at baseline (grade 0) were considered. After 12 weeks, the proportion of patients in remission was 82% (95% confidence limits 70% - 94% in the pantoprazole and 55% (95% confidence limits 33% - 77%) in the placebo treatment group, p=O.036. Adverse events were reported in 4% and 6% of patients in pantoprazole and placebo treatment groups, respectively CONCLUSIONS Pantoprazole 40 mg once daily was well tolerated and is more effective than placebo in the prevention of peptic ulcers in patients with rheumatic diseases who require continuous, long-term, treatment with NSAIDs.

Small bowel capsule endoscopy in clinical practice: a multicenter 7-year survey

Background and aim Data about small bowel capsule endoscopy (SBCE) come from studies involving small and highly selected populations. The study aim was to describe extent of use, indications, results, complications, and practical issues of SBCE in clinical practice in a Northern Italian Region (Lombardia). Materials and methods Twenty-three out of 29 invited centers fulfilled a specific questionnaire. Results Between 2001 and 2008, 2921 procedures were performed and both the number of centers performing SBCE (from 5 to 29) and the number of SBCE (from 7.2 to 69.2 per month) increased steadily. The main indications for SBCE were: obscure gastrointestinal bleeding (OGIB) (43.4%), unexplained anemia (23.9%), suspected Crohns disease (7.8%) and abdominal pain (5.3%). Overall, SBCE was positive in 50% of cases, negative in 36% and undefined in 14%. The highest diagnostic yields were observed in patients with OGIB (62.5%), polypoid syndromes (74.1%), known (54.8%) or suspected (47.3%) inflammatory bowel disease, while the yields were low in patients examined for chronic diarrhea (27.4%) and abdominal pain (14.9%), 61 patients (2.1%) experienced capsule retention. Thirty-two of them eventually excreted the capsule naturally while endoscopic or surgical retrieval was necessary in 29 (1%) (in two because of obstruction). Conclusion Over a period of 7 years the use of SBCE in Lombardia increased steadily confirming, in clinical practice, a high diagnostic yield and an acceptable safety profile.

HLA and autoimmune digestive disease: a clinically oriented review for gastroenterologists.

OBJECTIVES:The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice.METHODS:Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008.RESULTS:The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease.CONCLUSIONS:The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

Objective:The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity.Design:Double blind controlled study.Subjects:Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1±4.89 kg, mean body mass index (BMI) 43.6±1.09 kg/m2) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration.Measurements:We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test).Results:The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11±1.09 vs 5.7±1.1 kg, P<0.001) and BMI reduction (4±0.36 vs 2±0.58 kg/m2, P<0.001) and a higher satiety score on a visual analogic scale (7.63±0.38 vs 4.72±0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6±48 vs 139±31, P<0.001) and a greater prolongation in gastric emptying time (+18.93±8 vs −2.2±6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found.Conclusions:Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

Cigarette smoking, gastric acid secretion, and serum pepsinogen I concentrations in duodenal ulcer patients.

Cigarette smoking has been linked with duodenal ulcer disease although the mechanism of this association is unclear. This study assessed basal gastric secretory response to acute smoking of smokers with an active duodenal ulcer; in addition the possible effects of chronic smoking on gastric secretory capacity, as expressed by pentagastrin stimulated gastric acid secretion and fasting serum pepsinogen I (PG I) concentrations, were investigated in patients with active duodenal ulcer, or non-ulcer dyspepsia. In 10 smokers with duodenal ulcer smoking four cigarettes during 40 minutes did not influence basal gastric secretion of acid and pepsin, or serum PG I and gastrin concentrations. In 136 patients with duodenal ulcer and 90 controls with non-ulcer dyspepsia, pentagastrin stimulated acid secretion and fasting serum PG I concentrations were significantly higher among habitual heavy smokers than among non-smokers. These findings suggest that in heavy smokers with duodenal ulcer acid- and pepsin-secreting cell function is not affected by acute cigarette smoking. By contrast, chronic cigarette smoking seems to be associated either with an increase of parietal- and chief-cell mass, or with an enhancement of their secretory capacity.

Efficacy and tolerability of polyethylene glycol‐electrolyte lavage solution with and without simethicone in the preparation of patients with inflammatory bowel disease for colonoscopy

This placebo‐controlled study assessed the efficacy and tolerability of polyethylene glycol‐electrolyte lavage solution (PEG‐ELS), with and without simethicone, in the preparation of patients with inflammatory bowel disease for colonoscopy. PEG‐ELS 4 L plus placebo, or PEG‐ELS 4 L plus simethicone 120 mg, was administered according to a randomized double‐blind protocol to 115 patients with ulcerative colitis or Crohns disease. The parameters assessed were: presence of bubbles, degree of haziness, degree of bowel cleansing and patient acceptance. In the 105 patients completing the study, the efficacy of colonic lavage was found to be essentially comparable for the two preparations, although the addition of simethicone showed a significant reduction in the formation of bubbles. Significantly better results were reported by patients treated with the drug combination regarding reduction of general malaise (P= 0.01) and sleep disturbance (P= 0.01).

Eradication of Helicobacter pylori and long-term outcome of functional dyspepsia. A clinical endoscopic study.

The aim of this study was to assess the effect of colloidal bismuth subcitrate (CBS) and metronidazole on Helicobacter pylori eradication and on the course of symptoms due to functional dyspepsia. Forty-one patients with functional dyspepsia were entered into the study and randomized to treatment with CBS (120 mg four times a day) for four weeks combined with metronidazole (250 mg four times a day) for one week (group A,N=21) or matching placebo (group B,N=20). The severity of gastritis and of bacterial colonization and the symptom score was assessed by endoscopy and clinical evaluation at baseline and after four, eight, and 24 weeks from the start of the treatment. With intent-to-treat analysis eradication was achieved in 16/25 (64%) patients in group A and in 6/24 (25%) in group B. At eight and 24 weeks the gastritis score was significantly lower only in those patients with eradication. No change was seen in patients in whom the bacteria was not eradicated. The symptom score at eight weeks was considerably lower both in patients with eradication and in those with infection. However, at 24 weeks a gradual decrease in the symptom score in patients with eradication and a worsening of symptoms in controls was observed. No differences were observed between patients with ulcerlike and those with dysmotility-like dyspepsia. The study confirms the need for a long observation period after antibacterial treatment in patients with functional dyspepsia and suggests thatHelicobacter pylori-eradicating treatment improves the course of this functional syndrome.