Antonio Cuomo

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori

Abstract Background & Aims: The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains. This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H. pylori infection. Methods: We studied 150 consecutive H. pylori -infected dyspeptic subjects. Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing. H. pylori status was reevaluated 12 weeks after the end of treatment by the 13 C-urea breath test. Results: Susceptibility testing-based regimens led to the following results. (1) Eradication rates were 97.3% (95% confidence interval [CI], 91.2%–99.5%) (71 of 73) and 94.6% (95% CI, 87.6%–98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively. These were significantly higher ( P Conclusions: Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H. pylori infection.

Vascular endothelial growth factor and neo-angiogenesis in H. pylori gastritis in humans.

Host response plays a major role in the pathogenesis of Helicobacter pylori‐induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori‐infected and H. pylori‐non‐infected dyspeptic patients. Fifteen H. pylori‐infected and 15 H. pylori‐non‐infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT‐PCR. VEGF localization in the gastric mucosa and neo‐angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori‐infected than in non‐infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori‐infected mucosa than in the non‐infected mucosa. The increase in VEGF expression was associated with a significant increase in neo‐angiogenesis as assessed by determination of CD34‐positive micro‐vessels. H. pylori gastritis is therefore associated with up‐regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo‐angiogenesis may contribute to H. pylori‐related gastric carcinogenesis. Copyright

Vascular endothelial growth factor and cyclooxygenase-2 are overexpressed in ileal pouch-anal anastomosis

PurposePathophysiology of pouchitis after ileal pouch-anal anastomosis is controversial because of the potential for development of carcinoma. Cyclooxygenase-2-derived prostaglandins may be involved in the inflammatory process and play a role in the pathogenesis of colon cancer. Vascular endothelial growth factor plays a major role in neoangiogenesis and is overexpressed in a number of gastrointestinal malignancies. The goal of this study was to evaluate the expression of cyclooxygenase-2 and vascular endothelial growth factor and to assess neoangiogenesis and epithelial cell proliferation in patients with ileal pouch-anal anastomosis.MethodsEndoscopic biopsies were obtained from 15 patients with ileal pouch-anal anastomosis without pouchitis (10 biopsies from the ileal pouch and 10 from ileal nonpouch mucosa) and from 15 subjects with irritable bowel syndrome (10 biopsies from normal-appearing ileum and rectum). Cyclooxygenase-1, cyclooxygenase-2, and vascular endothelial growth factor messenger ribonucleic acid expression was determined by reverse transcriptase polymerase chain reaction. Cyclooxygenase-2 and vascular endothelial growth factor protein expression was evaluated by Western blot. Cyclooxygenase-2, vascular endothelial growth factor, CD34 (neoangiogenesis marker), and Ki67 (proliferation marker) mucosal localizations were evaluated by immunohistochemistry.ResultsExpression of cyclooxygenase-2 and vascular endothelial growth factor was increased in ileal pouch mucosa compared with ileal nonpouch mucosa, normal ileum, and rectum. Cyclooxygenase-2 and vascular endothelial growth factor immunostaining in ileal pouch mucosa was more intense in the crypt area than in the surface epithelium compared with ileal nonpouch mucosa. CD34 (neoangiogenesis marker) and Ki67 (proliferation marker) expression was increased in ileal pouch mucosa.ConclusionsCyclooxygenase-2 and vascular endothelial growth factor are overexpressed in the ileal pouch mucosa. This is associated with increased proliferative activity and neoangiogenesis. Cyclooxygenase-2 and vascular endothelial growth factor overexpression might play a role in the pathogenesis of pouchitis.

Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of

BACKGROUND & AIMS The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains. This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H. pylori infection. METHODS We studied 150 consecutive H. pylori-infected dyspeptic subjects. Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing. H. pylori status was reevaluated 12 weeks after the end of treatment by the (13)C-urea breath test. RESULTS Susceptibility testing-based regimens led to the following results. (1) Eradication rates were 97.3% (95% confidence interval [CI], 91.2%-99.5%) (71 of 73) and 94.6% (95% CI, 87.6%-98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively. These were significantly higher (P < 0.005) than eradication rates obtained without susceptibility testing, that is, 79.4% (95% CI, 69.1%-87.6%) (58 of 73) and 77.3% (95% CI, 66.9%-85.7%) (58 of 75) in the per-protocol and intention-to-treat analyses, respectively. (2) There were savings of approximately

Coeliac disease and C virus-related chronic hepatitis: a non association

5 U.S. per patient compared with standard triple therapy. CONCLUSIONS Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H. pylori infection.

Present and future of metastatic colorectal cancer treatment: A review of new candidate targets

BackgroundA higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C.Materials and methodsTwo hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent.Results1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological.Conclusions1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Multi Matrix System Mesalazine Plus Rectal Mesalazine in the Treatment of Mild to Moderately Active Ulcerative Proctitis

In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer (mCRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with mCRC. In this review, we describe approved targeted therapies for the management of metastatic mCRC and discuss new candidate targets on the horizon.

Pharmacotherapy of Helicobacter pylori -associated gastritis

Background: Mesalazine 1 g suppository/die is used for mild to moderately active ulcerative proctitis (UP). Whether addiction of Multi Matrix System (MMX) mesalazine increases the remission rate of UP and prevents proximal extension of disease is unknown. Methods: This is a retrospective study on 116 outpatients with UP who had been treated with one of the following regimens: (1) MMX mesalazine 1.2 g/die plus mesalazine suppositories for 8 ± 2 weeks and, subsequently, MMX mesalazine 1.2 g/die plus rectal mesalazine 1 g every other day for at least 6 months; (2) mesalazine 1 g suppositories/die alone for 8 ± 2 weeks and, subsequently, rectal mesalazine 1 g every other day for 6 more months. Patients were evaluated clinically at 2 months (±2 weeks) and endoscopically at 6 months (±2 weeks). For categorical variables, Pearson chi-square test was used. Results: A total of 46 of 55 patients (84%) on combined therapy and 49 of 61 patients (80%) on rectal mesalazine reached clinical remission (p > 0.05; OR 0.79, 95% CI 0.30–2.07). At 6 months follow-up, proximal extension of disease was observed in 7 of 55 (14%) patients on combined therapy and in 18 of 61 (29%) patients on rectal mesalazine alone (p < 0.05; OR 2.87, 95% CI 1.09–7.53). Conclusions: Oral MMX mesalazine plus rectal mesalazine combined treatment is associated with prevention of proximal extension of the disease compared with rectal mesalazine alone.

Eradication of Helicobacter pylori: A Clinical Update

Helicobacter pylori (H. pylori) is a ubiquitous gram-negative bacterium infecting half the worlds population [1, 2]. Transmission occurs via person-to-person passage, and unclean water sources have been implicated in infection transmission. The principal reservoir is the human stomach. Prevalence rates are much higher in developing countries and generally vary by geographical location, ethnic race, socio-economic conditions, and age.