Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: a large, multicentre study.

BACKGROUND: Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice. STUDY DESIGN: This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis. RESULTS: Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P < 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device. CONCLUSION: The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications.

Real-time determination of gastric juice pH with EndoFaster® for atrophic gastritis assessment.

BACKGROUND: In patients with atrophic gastritis involving gastric body mucosa the pH value of gastric juice is distinctly increased, so that pH assessment would allow predict this precancerous lesion. We tested whether EndoFaster® - a device allowing real-time pH measure and H. pylori diagnosis - may optimize the need of taking gastric biopsies. METHODS: In this prospective, multicentre study, the accuracy of EndoFaster® for ruling out gastric atrophy involving corporal mucosa was assessed. Real-time pH and ammonium determination was performed by aspirating 3-6 ml gastric juice during endoscopy. Histology performed on 5 standard gastric biopsies was used as gold standard. RESULTS: A total of 1008 consecutive patients were observed in 12 centres. At histology, gastric body mucosa atrophy/metaplasia was detected in 65 (6.4%) cases, and a pH value >4.5 in the gastric juice was observed in 150 patients. The values of EndoFaster® performance in predicting the presence of atrophic gastritis were as follow: 51% sensitivity, 84% specificity, 18% PPV, 96% NPV, and 82% accuracy. The NPV value was not distinctly affected by neither ongoing proton pump inhibitor therapy nor H. pylori infection. By considering also data of ammonium concentrations, the values of EndoFaster® in detecting extensive atrophy on gastric mucosa were 74% sensitivity, 84% specificity, 24% PPV, 98% NPV, and 83% accuracy. CONCLUSION: The very high NPV of EndoFaster® might allow to safely rule out presence of atrophic gastritis, reducing the need of taking gastric biopsies in unselected patients managed in clinical practice.

Evaluation of Antibiotic Resistance of Helicobacter pylori Strains Isolated in Bari, Southern Italy, in 2017-2018 by Phenotypic and Genotyping Methods.

Objective: Helicobacter pylori antibiotic resistance is a constantly evolving process and local surveillance is warranted to guide clinicians in the choice of therapy. Materials and Methods: Antibiotic susceptibility testing was performed by E-test on 92 H. pylori strains, and resistance to clarithromycin and levofloxacin was also evaluated using a commercially available genotyping method. Results: In naïve patients the resistance to clarithromycin, levofloxacin, and metronidazole was 37.7%, 26.2%, and 16.4%, respectively, significantly lower than the percentage found in treated patients. Concomitant resistance to ≥2 antibiotics was also observed in naïve patients. The A2143G mutation of the 23S-rRNA gene was the most frequently detected, also in naïve patients. The highest minimum inhibitory concentration (MIC)50 value (256 mg/L) was associated with A2142 mutations in all the patients carrying them. For levofloxacin resistance a mutation in codon 87 was detected in 63.9% and in codon 91 in 36.1% of the H. pylori strains, without significant differences in the patients groups. A mutation in codon 87 was associated with the highest MIC50 value (32 mg/L). Conclusions: In our area, a high prevalence of H. pylori primary resistance was detected; these rates were higher in patients who had experienced failure of several courses of therapy. A better knowledge of the local epidemiology of resistance, and the genotypes responsible, will improve the H. pylori eradication rates.

Early radiation-induced mucosal changes evaluated by proctoscopy: predictive role of dosimetric parameters.

BACKGROUND AND PURPOSE: Late rectal complications are assessed according to different scoring systems. Endoscopy can provide a more sensitive estimation of early radiation damage. The aim of this paper is to investigate the correlation between dosimetric parameters and rectal mucosal changes after radiotherapy (RT). MATERIALS AND METHODS: Patients with prostate adenocarcinoma treated with curative or adjuvant RT underwent endoscopy 1 year after RT. Receiver operating characteristics (ROC) analysis was performed to analyze the predictive capability of the dosimetric variables in determining mucosal changes classified by Vienna Rectoscopy Score (VRS). RESULTS: The best dosimetric predictors of grade ≥2 telangiectasia were rectal (r) V(60 Gy) (p=0.014), rV(70 Gy) (p=0.017) and rD(mean) (p=0.018). Similar results were obtained for grade ≥2 VRS. The set of rV(60 Gy)<34.4%, rV(70 Gy)<16.7% and rD(mean)<57.5 Gy was associated with a decreased risk of grade ≥2 telangiectasia and VRS. CONCLUSIONS: rV(60 Gy), rV(70 Gy) and rD(mean) were the strongest predictors of rectal mucosal alterations. In-depth analysis is required to correlate each mucosal alteration with late rectal toxicity in order to suggest early proctoscopy as surrogate end-point for rectal late toxicity in studies aimed at reducing this important complication.

Barrett's esophagus and esophageal cancer: an overview.

Although esophageal cancer (EC) is the eighth most common cancer in several European countries, it is one of deadliest worldwide. The most frequent predisposing factor implicated in its development is Barrett's esophagus (BE), an acquired metaplastic transformation of the esophageal lining cells from normal squamous epithelium into specialised or intestinal-like columnar epithelium. The major risk factor for BE is gastroesophageal reflux disease. Although BE is in itself a benign and often asymptomatic disorder, its clinical importance stems from the recognition that it represents the main precursor lesion for the development of esophageal adenocarcinoma (AC), a tumor that is rapidly increasing especially in developed countries and is associated with a low survival rate. This paper provides an overview of the epidemiology and natural history of BE as well as of the possible pathogenetic mechanisms underlying the development of BE and its progressive transition to AC. New diagnostic tests are described, recommendations for screening and surveillance are provided and surgical and ablative procedures to treat dysplastic lesions and early neoplasia are discussed. Claimed chemopreventive agents and biomarkers that in the near future may help identify people with a higher risk of EC are also considered.

Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis.

BACKGROUND: It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders. Aim of the study A 'post-hoc' retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing. MATERIAL AND METHODS: Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2-3 to 0. ANOVA plus Student-Newman-Keuls was used for statistical analysis. RESULTS: The authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls. CONCLUSIONS: Balanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.

Differential immunohistochemical expression of syndecan-1 and tumor necrosis factor alpha in colonic mucosa of patients with Crohn's disease.

Tumor necrosis factor alpha (TNFalpha) in intestinal mucosa plays a key role in the inflammation characterizing Crohn's disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFalpha and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFalpha and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFalpha and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFalpha in CD. In conclusion, TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.

Gastric epithelial cell proliferation and ras oncogene p21 expression in first-degree relatives of gastric cancer patients: a case-control study.

OBJECTIVES: Individuals with a family history of gastric cancer have an increased risk of developing such neoplasia. This study aimed to assess epithelial cell proliferation and ras oncogene mutation in such individuals. METHODS: Twenty dyspeptic, first-degree relatives of patients with gastric cancer and 20 matched controls were enrolled. Endoscopy with biopsies was performed in all cases. Gastric specimens were used to look for Helicobacter pylori infection and to assess both epithelial cell proliferation and ras oncogene expression by immunohistochemistry. RESULTS: Cell proliferation values were not significantly different between the patient and control groups (18.1 +/- 7.1 versus 18.9 +/- 7.4; P = 0.7). Overall, ras mutation was detected in five out of 40 cases, and its distribution was similar between patients and controls (20 versus 10%; P = 0.9), as well as between H. pylori-positive and negative patients (22 versus 9%; P = 0.2). Cell proliferation values tended to be higher in cases with ras mutation than in those without (25.2 +/- 9.4 versus 16.8 +/- 5.8; P = 0.08). Cell proliferation values were significantly higher in H. pylori-positive cases compared with uninfected cases, in both patient (24.7 +/- 4.7 versus 12.5 +/- 2.4; P = 0.0003) and control (25.9 +/- 4.8 versus 13.3 +/- 2.8; P = 0.0003) groups. CONCLUSIONS: Both gastric cell proliferation values and ras mutation prevalence did not differ between first-degree relatives of gastric cancer patients and controls. H. pylori infection similarly increased the proliferation index of gastric mucosa in both groups.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

BACKGROUND: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. DESIGN: Post hoc subgroup study from a multicenter, randomized trial. SETTING: Two hospitals in central and southern Italy between January and December 2001. PATIENTS: 156 patients with H. pylori infection. MEASUREMENTS: Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. INTERVENTION: 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. RESULTS: Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). LIMITATIONS: The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (70 euros per patient). CONCLUSIONS: The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.