Peptic ulcer and Helicobacter pylori: update on testing and treatment.

As evidence about the relationship between Helicobacter pylori infection and peptic ulcers accumulates, accurate testing and treatment are becoming increasingly important. However, big questions remain about the best strategies for detecting and managing this infection. In this article, the authors discuss the association between H pylori and peptic ulcer disease, the available tests for detecting the infection, and the latest treatment strategies for effective eradication.

[Non-invasive analyses for the diagnosis of Helicobacter pylori infection. A critical review of the literature]. / Test non invasivi per la diagnosi di infezione da Helicobacter pylori. Revisione critica della letteratura.

Helicobacter pylori (H. pylori) infection may be diagnosed by means of invasive techniques requiring endoscopy and biopsy (histological examination, rapid urease test, culture, polymerase chain reaction) and by non-invasive techniques (urea breath test, detection of specific antibodies in the serum or urine, detection of the H. pylori antigen in a stool specimen). Some non-invasive tests detect active infection e.g. the urea breath test and the stool antigen test and are called active tests. Other non-invasive tests are markers of exposure to H. pylori (e.g. serology or urine) but do not indicate whether active infection is ongoing and are called passive tests. Non-invasive tests and treatment strategies are widely recommended in primary care settings and the choice of the appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness. The available non-invasive tests are reviewed in this article.

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux.

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%, P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

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.

Serological markers for gastric atrophy in asymptomatic patients infected with Helicobacter pylori.

OBJECTIVE: Atrophic gastritis is a precancerous condition that is commonly caused by chronic Helicobacter pylori (H. pylori) infection. This blinded, controlled study was designed to determine if serum gastrin and pepsinogens were reliable markers of atrophy in asymptomatic patients. METHODS: One hundred and forty-seven asymptomatic patients underwent endoscopy with multiple gastric biopsies obtained for histology, culture, and rapid urease test. Fasting serum gastrin (total and G-17) and serum pepsinogens (I-II) were determined by standard immunoassays. Gastric atrophy was histologically assessed in accordance with internationally accepted criteria; three main patterns of gastritis were distinguished: (a) nonatrophic gastritis, (b) atrophic antrum-restricted and antrum-predominant gastritis, and (c) corpus-restricted gastritis. Receiving operating characteristic (ROC) analysis was used to determine the best cut-off for each serum test in nonatrophic gastritis versus antrum-restricted/antrum-predominant atrophic gastritis. RESULTS: No significant differences in serum gastrin and pepsinogens I-II were detected in nonatrophic gastritis versus patients with antrum-restricted/antrum-predominant atrophic gastritis. The positive likelihood ratios for an abnormal serum test to detect antrum-restricted/antrum-predominant atrophy in the gastric body were total serum gastrin 2.13 (95% CI 0.99, 4.6), gastrin-17: 1.55 (95% CI 0.75, 36.17), pepsinogen I: 2.74 (1.4, 5.4), pepsinogen II: 1.74 (1.27, 2.39), and the ratio of pepsinogen I and II: 1.8 (1.2-2.8). Negative likelihood ratios ranged from 0.20 to 0.65. CONCLUSION: In an asymptomatic population, serum gastrin (total and G-17) and pepsinogens I-II (and their ratio) do not discriminate nonatrophic versus antrum-restricted/predominant atrophic gastritis.

Effect of proton pump inhibitors and antacid therapy on 13C urea breath tests and stool test for Helicobacter pylori infection.

OBJECTIVE: There is uncertainty about the best method of testing patients for Helicobacter pylori (H. pylori) infection while they are taking proton pump inhibitors. The aim of this study was to determine: (i) if the decreased sensitivity of the urea breath test during proton pump inhibitor is corrected by different techniques for breath testing and (ii) if the sensitivity of stool test is decreased with the administration of proton pump inhibitors. METHODS: Prospective randomized single-blind study was performed in a tertiary care university hospital. Out of 72 H. pylori infected patients endoscoped for upper abdominal symptoms 48 were randomized to proton pump inhibitors (omeprazole 20 mg each day or esomeprazole 40 mg each day) and 24 to antacid (aluminum hydroxide 800 mg each day) for 14 days. Several breath tests (standard 75 mg (13)C-UBT with citric acid, with orange juice, a tablet breath test with 100 and 50 mg of (13)C), and a stool test were carried out. Baseline samples were collected before and after treatment. RESULTS: The baseline sensitivity for all breath tests was 100% in both groups; for stool test it was 97.8% (95% CI: 88.7-96.6) and 90% (95% CI: 69.9-97.2) in the proton pump inhibitor and antacid group, respectively. After treatment, the sensitivity of tests was significantly low (UBTs range: 77.1%-85.4%; stool test: 83%; 95% CI: 63.9-91.1), while it was unchanged in the antacid group. CONCLUSIONS: False negative breath and stool tests are equally common in patients taking proton pump inhibitors. Antacids do not impair the sensitivity of the breath tests or the stool test.

Susceptibility of Helicobacter pylori to metronidazole.

OBJECTIVES: The reliability of the Epsilometer-test (E-Test) and the disk diffusion (DD) method in the assessment of susceptibility of Helicobacter pylori (H. pylori) to metronidazole has recently been questioned, with possible clinical implications for the management of patients undergoing H. pylori eradication. The aims of this study were: 1) to compare the E-Test and disk diffusion methods to the agar dilution method for determining the susceptibility of H. pylori to metronidazole; and 2) to investigate whether potential discrepancies could be caused by the simultaneous presence of metronidazole susceptible and metronidazole resistant bacterial subpopulations. METHODS: A total of 109 H. pylori strains from 121 consecutive patients were examined. All tests were carried out at the same time starting from primary plates. Agar dilution was performed according to National Committee for Clinical Laboratory Standard (NCCLS) standards, the E-Test according to the manufacturer's guidelines, and disk diffusion according to standard procedure using 5-mug metronidazole disks. Isolates were considered to be metronidazole resistant if the minimal inhibitory concentration was >8 mug/ml for the agar dilution and the E-Test, or if the inhibition zone around the disk was <20 mm for disk diffusion. Of 109 isolates, 43 were also investigated to detect mixed infection. Quantities of 100 mul of bacterial suspensions of each strain were seeded onto plain agar plates and plates containing 8 mug/ml of metronidazole. Cultures were considered to be mixed if the number of colonies on agar plates exceeded by at least 30% those on the metronidazole plates. RESULTS: According to agar dilution, 57 strains (52.3%, 95% CI = 43-61.4) were metronidazole resistant. E-Test misdiagnosed two strains that were considered sensitive to metronidazole, but according to the agar dilution test they were resistant. Disk diffusion misdiagnosed three strains. Two of these strains (the same as the E-Test) were sensitive, but according to agar dilution they were metronidazole resistant; the third strain was resistant, but according to agar dilution it was sensitive. The percentages of discordance were 1.9 (95% CI = 0.5-6.6) and 2.8 (95% CI = 0.9-7.8), respectively, when the E-Test and disk diffusion were compared to agar dilution. Intertest variability among agar dilution and the E-Test showed that 39.4% (95% CI = 30.8-48.8) of minimal inhibitory concentrations were equivalent (within +/-1 log(2)), 60.6% (95% CI = 51.2-69.2) were major errors (more than +/-1 log(2)), and 3% (95% CI = 0.8-10.4) were very major errors (change in susceptibility pattern). Mixed infection was found in six of the 43 cases examined (13.9%). In four cases, metronidazole resistant strains were 1 log(10) less numerous than those that were metronidazole susceptible. In the remaining two cases, the metronidazole resistant strains were 2-3 log(10) less numerous, which caused the two misdiagnoses. CONCLUSIONS: The E-Test and disk diffusion method are very good alternatives to agar dilution. Mixed infections are a possible cause of the discrepancies between these tests and the reference method.

Peroxidation potential of lipid emulsions after compounding in all-in-one solutions.

OBJECTIVES: We investigated the peroxidation potential of fat emulsions in all-in-one solutions (AIOs). METHODS: Three 20% emulsions were compared: soybean oil (SO; 60% polyunsaturated fatty acids [PUFAs], alpha-tocopherol:PUFAs = 0.44), soybean plus medium-chain triacylglycerol (SO-MCT; 31% PUFAs, alpha-tocopherol:PUFAs = 0.35), and olive oil (OO; 21% PUFAs, alpha-tocopherol:PUFAs = 1.42). For each emulsion, six AIO solutions were prepared by adding 250 mL of emulsion to a lipid-free solution. Lipid peroxide (LPX) and malondialdehyde (MDA) concentrations were evaluated in fat emulsions, lipid-free solutions, and AIOs immediately (T0) and 24 h (T24) after lipid addition. Statistical analysis was done with analysis of variance. RESULTS: Fat emulsion LPX in SO-MCT was lower than that in SO (P = 0.015) and OO (P = 0.024); LPX in SO was greater than that in OO (P = 0.013); MDA in SO was greater than that in SO-MCT (P = 0.001) and OO (P = 0.013); and MDA in SO-MCT was greater than that in OO (P = 0.001). In comparison with MDA at AIO-T0, MDA at AIO-T24 increased in SO (P = 0.005) and SO-MCT (P < 0.001) and decreased in OO (P = 0.003); at AIO-T24, LPX was greater in SO, but not significantly. CONCLUSIONS: In AIO bags, LPX occurred within 24 h after the addition of the lipid emulsion and seemed to be directly related to the PUFA content and inversely related to the alpha-tocopherol:PUFA ratio of the emulsion.

Effect of Levovist on splanchnic hemodynamics in cirrhotic patients.

This study was aimed to assess the effect of Levovist on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 +/- 0.07 vs. 0.71 +/- 0.06; p < 0.01) and splenic arteries (0.72 +/- 0.06 vs. 0.64 +/- 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase.

Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We have recently documented the efficacy of a highly concentrated probiotic preparation (VSL#3) in the prevention of flare-up in patients with chronic pouchitis. The aim of this study was to compare probiotic therapy with VSL#3 versus placebo in the ability to prevent the onset of acute pouchitis during the first year after ileal pouch-anal anastomosis. METHODS: Forty consecutive patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were randomized to receive either VSL#3 (1 packet containing 900 billion bacteria/day) (n = 20) or an identical placebo (n = 20) immediately after ileostomy closure for 1 year. The patients were assessed clinically, endoscopically, and histologically after 1, 3, 6, 9, and 12 months. Health-related quality of life was assessed using the Inflammatory Bowel Disease Questionnaire. RESULTS: Two of the 20 patients (10%) treated with VSL#3 had an episode of acute pouchitis compared with 8 of the 20 patients (40%) treated with placebo (log-rank test, z = 2.273; P < 0.05). Treatment with VSL#3 determined a significant improvement in Inflammatory Bowel Disease Questionnaire score, whereas this was not the case with placebo. CONCLUSIONS: Treatment with VSL#3 is effective in the prevention of the onset of acute pouchitis and improves quality of life of patients with ileal pouch-anal anastomosis.

Antimicrobial activity of esomeprazole versus omeprazole against Helicobacter pylori.

OBJECTIVE: Esomeprazole is an enantiomorph of omeprazole, which inhibits gastric acid secretion more effectively than omeprazole. As proton pump inhibitors also exert an antibacterial activity, we aimed to compare esomeprazole and omeprazole for their antimicrobial activity against Helicobacter pylori in vitro. METHODS: We studied 52 H. pylori isolates obtained from gastric biopsies and inoculated onto agar plates containing the acid-converted drugs at different concentrations. The minimal concentrations that inhibited the growth of 50% and 90% of isolates were defined as MIC(50) and MIC(90). RESULTS: The MIC(50) and MIC(90) of esomeprazole were 16 and 32 mg/L; and those of omeprazole were 32 and 64 mg/L. Overall, 63.5% of isolates showed the same susceptibility to both drugs; 17 isolates were two- to 64-fold more susceptible to esomeprazole and two isolates were two-fold more susceptible to omeprazole. CONCLUSIONS: The increased antimicrobial activity in vitro of esomeprazole against H. pylori could contribute to improving the outcome of the eradication treatment of such an infection.

The stool antigen test for detection of Helicobacter pylori after eradication therapy.

BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed. OBJECTIVE: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection. DESIGN: Prospective blinded study. SETTING: Six clinical centers in the United States and Europe. PATIENTS: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms. MEASUREMENTS: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy. RESULTS: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]). CONCLUSION: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.