L.G. Cavallaro

Efficacy of mesalazine in the treatment of symptomatic diverticular disease.

We aimed to improve symptoms by means of mesalazine in symptomatic colonic diverticular disease patients. One hundred seventy outpatients (98 M, 72 F; age, 67.1 years; range, 39–84 years) were assigned to four different schedules: rifaximin, 200 mg bid (Group R1: 39 pts), rifaximin, 400 mg bid (Group R2: 43 pts), mesalazine, 400 mg bid (Group M1: 40 pts), and mesalazine, 800 mg bid (Group M2: 48 pts), for 10 days per month. At baseline and after 3 months we recorded 11 clinical variables (upper/lower abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tenderness, fever, general illness, nausea, emesis, dysuria), scored from 0 = no symptoms to 3 = severe. The global symptomatic score was the sum of all symptom scores. After 3 months in all schedules but Group R1, 3 of the 11 symptoms improved (P < 0.03); the global score decreased in all groups but Group R1 (P < 0.0001). Mesalazine-treated patients had the lowest global score at 3 months (P < 0.001). Mesalazine is as effective as rifaximin (higher dosage schedule) for diminishing some symptoms, but it appears to be better than rifaximin for improving the global score in those patients.

Non-invasive tests in gastric diseases

Although the gastric cancer incidence is decreasing, this neoplasia remains one of the major causes of oncological mortality. Because of an insidious development, gastric cancer is often diagnosed in an advanced stage and consequently with a poor prognosis. Accurate non-invasive tests should be extremely useful in order to detect gastric neoplasm in an early phase. In clinical practice, there is no reliable bio-marker for detecting this malignant disease. However, intestinal as well as diffuse types of gastric cancer are preceded by gastric mucosa inflammation. Furthermore, the intestinal type of the neoplasia is, generally, related to chronic atrophic gastritis, especially if associated with intestinal metaplasia. In particular, the risk of the neoplasm is linked to both extension and severity of gastric atrophy. Serological parameters such as serum pepsinogens I (PGI) and II (PGII), gastrin-17 (G-17) cytokines (e.g. IL-8), antiparietal cells, IgG anti-Hp and CagA antibodies and lastly ghrelin supply information about either atrophic or inflammatory conditions characterising gastric mucosa. Low PGI and PGI/PGII ratio levels, especially if combined with high G-17 levels, are recognised bio-markers of corpus atrophic gastritis. Low G-17 levels could be, also, suggestive of antral atrophic gastritis. Furthermore, plasmatic ghrelin levels seem to be also a bio-marker of corpus atrophy. Anti-Hp IgG and CagA antibodies as well as PGII levels are able to detect gastric inflammation. Serological parameters could select subjects at risk for gastric mucosa alterations such as inflammation or atrophy, rather than gastric cancer itself. This review analyses the information derived from serological bio-markers as well as the involved clinical studies.

A Curcumin-Based 1-Week Triple Therapy for Eradication of Helicobacter pylori Infection: Something to Learn From Failure?

Background:  Curcumin is the principal element of turmeric powder extracted from the root of Curcuma longa. Studies on curcumin have demonstrated some anti‐Helicobacter pylori activity as well as immunomodulating properties. N‐acetylcysteine and lactoferrin with their respective mucolytic and antibacterial activities might also be effective in H. pylori eradication therapy.

Use of bovine lactoferrin for Helicobacter pylori eradication

BACKGROUND One-week triple therapy is the most frequently recommended treatment for Helicobacter pylori infection. Eradication rate is satisfactory, nevertheless is advisable to look for more effective therapies. AIM To test the efficacy of a standard triple therapy plus bovine lactoferrin in the eradication of H. pylori infection. PATIENTS AND METHODS One hundred and fifty consecutive H. pylori positive patients, suffering from dyspeptic symptoms were recruited in a 7-day triple therapy open randomised single centre study with rabeprazole, clarithromycin, tinidazole, bovine lactoferrin (group A) or rabeprazole, clarithromycin, tinidazole (group B), or a 10-day therapy with rabeprazole, clarithromycin, tinidazole (group C). H. pylori status was assessed 8 weeks after the end of the treatment by means of a 13C-urea breath test or a H. pylori stool antigen-test. RESULTS Eradication rates (intention to treat/per protocol) were: group A (92.2/95.9%), group B (71.2/72.5%) and group C (70.2/75%). The efficacy of triple therapy added with lactoferrin was significantly higher than other two regimens (p=0.01, intention to treat analysis; p=0.005, per protocol analysis). CONCLUSION These results suggest that lactoferrin tested in the present study was effective in curing H. pylori and could be a new agent to assist the antimicrobials in the eradication of the bacterium.

Quality of Life in Uncomplicated Symptomatic Diverticular Disease: Is It Another Good Reason for Treatment?

Background: Quality of life (QoL) is becoming a major issue in the evaluation of any therapeutic intervention. Aims: To assess the QoL in patients with uncomplicated symptomatic diverticular disease (DD) and to elucidate the influence of two different treatments either on symptoms or QoL. Materials and Methods: 58 outpatients affected by uncomplicated symptomatic DD, admitted in our Gastroenterological Unit from October 2003 to March 2004, were enrolled. Patients were randomly assigned to two different treatments consisting of rifaximin or mesalazine for 10 days every month for a period of 6 months. QoL was evaluated by means of an SF-36 questionnaire and clinical evaluation was registered by means of a global symptomatic score (GSS) at baseline and after 6 months. Results: At baseline, lower values in all SF-36 domains were confirmed in patients with DD. Both rifaximin and mesalazine groups showed a significant reduction of their mean GSS (p < 0.01 and p < 0.001, respectively) and improvement of SF-36 mean scores after therapy, even though treatment with mesalazine showed better results. Conclusions: DD has a negative impact on QoL. Cyclic treatment with poorly absorbable antibiotics or anti-inflammatory drugs relieves symptoms and improves QoL.

'Rescue' Therapies for the Management of Helicobacter pylori Infection

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7–14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient’s compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10–14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = –0.33, P < .001) and intestinal metaplasia (r = –0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

Bovine lactoferrin for Helicobacter pylori eradication: an open, randomized, multicentre study.

Background  Cure rates for eradication of Helicobacter pylori appear to be decreasing, thus more effective therapies must be identified.

'Serological biopsy' in first-degree relatives of patients with gastric cancer affected by Helicobacter pylori infection.

Background: Relatives of patients with gastric cancer are at increased risk of developing this disease, especially if they are infected by Helicobacter pylori. Moreover, H. pylori‐related atrophic gastritis and hypochlorhydria are well‐documented risk factors for noncardia gastric cancer. Serum pepsinogen I (sPGI) and II (sPGII) levels are low in this condition. The aim of our study was to assess by means of a ‘Gastropanel’ blood test, including sPGI, sPGII, gastrin‐17 (G‐17) and antibodies anti‐H. pylori (IgG‐Hp), both functional and morphological features of gastric mucosa in Hp + ve subjects with a family history of gastric cancer. Materials and Methods: Twenty‐five Hp + ve subjects consecutively referred to our department for gastrointestinal complaints, selected as first‐degree relatives of patients suffering from gastric cancer, were enrolled in the study and then matched for sex and age with 25 dyspeptic and Hp + ve subjects with no family history of gastric neoplasia. Blood samples were taken for determination of gastropanel in all patients; in addition, antibodies against CagA were analysed. Results: No statistically significant differences were detected zbetween the two groups as regards alcohol consumption, coffee intake and smoking habits. Mean sPGI levels in Group A (83.4 ± 58.4 μg/L) were significantly lower than those in Group B (sPGI 159.5 ± 80.6 μg/L; P < 0.0001) as well as sPGII (12.5 μg/L ± 6.24 versus 20.6 ± 58 μg/L; P < 0.006). No statistical difference was found between the two groups in relation to G‐17 levels, IgG‐Hp titres and antibodies against CagA. Conclusion: First‐degree relatives of patients with noncardia gastric cancer affected by H. pylori infection present lower sPGI and sPGII levels, possibly due to the increased frequency of atrophic lesions in these patients.

Use of Mesalazine in Diverticular Disease

Diverticular disease includes a spectrum of conditions sharing the underlying pathology of acquired diverticula of the colon: symptomatic uncomplicated diverticular disease, recurrent symptomatic uncomplicated diverticular disease, and complicated diverticular disease. Goals of therapy in diverticular disease should be to improve symptoms and to prevent recurrent attacks in symptomatic uncomplicated diverticular disease, and to prevent the complications of disease such as diverticulitis. Inflammation seems to play a key role in all forms of the disease. This is the rationale for the use of anti-inflammatory drugs such as mesalazine. Inflammation in such diseases seems to be generated by a heightened production of proinflammatory cytokines, reduced anti-inflammatory cytokines, and enhanced intramucosal synthesis of nitric oxide. The mechanisms of action of mesalazine are not yet well understood. It is an anti-inflammatory drug that inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free radicals, and has an intrinsic antioxidant effect. Some recent studies confirm the efficacy of mesalazine in diverticular disease both in relief of symptoms in symptomatic uncomplicated forms and in prevention of recurrence of symptoms and main complications.