Mônica Maria Demas Álvares Cabral

Evaluation of [13C]urea breath test and Helicobacter pylori stool antigen test for diagnosis of H. pylori infection in children from a developing country.

ABSTRACT The [13C]urea breath test (13C-UBT) and Helicobacter pylori stool antigen test (HpSA) for the diagnosis of H. pylori infection in children were validated. The sensitivity, specificity, and positive and negative predictive values were 93.8, 99.1, 97.8, and 98.0%, respectively, for the 13C-UBT and 96.9, 100, 100, and 98.0%, respectively, for HpSA. Both tests are appropriate for diagnosing H. pylori infection in children.

Association of the Presence of Helicobacter in Gallbladder Tissue with Cholelithiasis and Cholecystitis

ABSTRACT The presence of Helicobacter DNA species has been investigated in the biliary epithelium of patients with biliary diseases. However, conflicting results have been observed that may have been due to the small number of subjects studied, difficulty in obtaining a healthy control group, absence of controlling for confounding factors, or differences among populations. Therefore, we investigated the presence of Helicobacter species by culture and nested PCR of 16S rRNA genes in gallbladder tissue and bile from 46 Brazilian subjects with and 18 without cholelithiasis. The control group was mainly composed of liver donors and of patients who had submitted to cholecystectomy as part of the surgical treatment for morbid obesity. No Helicobacter species were grown from the bile or gallbladder tissues. Helicobacter DNA was detected in the gallbladder tissue and bile from 31.3 and 42.9% of the patients, respectively. In a logistic regression model, cholelithiasis was positively and independently associated with the female gender (P = 0.02), increasing age (P = 0.002), and the presence of Helicobacter DNA in the gallbladder tissue (P = 0.009). The presence of Helicobacter DNA in the bile was not associated with cholelithiasis (P = 0.8). A significant association between the presence of Helicobacter DNA in the gallbladder epithelium and histological cholecystitis, even after adjusting for gender and age (P = 0.002), was also observed. The sequences of the 16S rRNA genes were >99% similar to that of Helicobacter pylori. In conclusion, our results support the hypothesis that Helicobacter is associated with the pathogenesis of human cholelithiasis and cholecystitis.

babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

ABSTRACT The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

Factors Associated with Helicobacter pylori Infection by a cagA-Positive Strain in Children

Although infection with a cagA-positive Helicobacter pylori strain is considered a risk factor for the development of duodenal peptic ulcer in adults, this association has not been demonstrated in children. The presence of cagA was investigated by polymerase chain reaction in H. pylori strains isolated from 27 children with duodenal ulcer and 53 without duodenal ulcer. All patients (100%) with duodenal ulcer and 33 (62.3%) without ulcer were colonized by a cagA-positive strain (P=.00007). A cagA-positive status was also associated with a more marked macroscopic gastritis, with a greater inflammatory infiltrate of both mononuclear and polymorphonuclear cells in the antral and oxyntic gastric mucosae and degenerative and regenerative changes of the gastric mucosa. Increased cagA positivity was also associated with increased age, but no association between cagA-positive status and sex was observed.

Standardized endoscopic submucosal tunnel dissection for management of early esophageal tumors (with video).

Endoscopic submucosal dissection (ESD) was first developed to remove en bloc early gastric neoplasms. Later, this technique was proposed for the management of esophageal and colorectal superficial tumors, and currently ESD is performed routinely in Asia. ESD is indicated for esophageal cancer with no or minimal risk of lymph node metastasis. When the lesions are classified according to the depth of invasion as intraepithelial carcinoma (M1), restricted within the proper mucosal layer (M2), adjacent to or invading but not beyond the muscularis mucosa (M3), invading the submucosal (SM) layer to a depth of one third (SM1) or more than one third (SM2 and SM3) of the layer thickness, then the incidence of lymph node metastasis was reported to be 0%, 0% to 5.6%, 8% to 18%, 11% to 53%, and 30% to 54%, respectively. Therefore, under the 2002 Japan Esophageal Society guidelines for the treatment of esophageal cancer, the absolute indication for endoscopic resection is defined as M1-M2 esophageal cancer as well as two thirds or less extension of the circumference, whereas the relative indication is defined as M3-SM1 esophageal cancer with as much as three fourths or more mucosal defect after resection. ESD with complete resection can only be considered curative for M1-M2 esophageal squamous cell

dupA polymorphisms and risk of Helicobacter pylori-associated diseases

The dupA of Helicobacter pylori has been suggested as a virulence marker associated with the development of duodenal ulcer disease. However, the studies performed in different geographical areas have shown that there are variations in the prevalence of dupA and its association with H. pylori clinical outcomes. Our group did not observe associations between the presence of dupA and H. pylori clinical outcomes in Brazil. On the other hand, we observed 2 mutations in the sequence of dupA that lead to stop codons: a deletion of an adenine at position 1311 and an insertion of an adenine at position 1426 of the gene. Our aim was to evaluate associations of the presence of dupA with duodenal ulcer and gastric cancer, considering dupA-positive only those H. pylori strains that do not have the mutations in the gene sequence. We also evaluated the effect of infection with a strain carrying an intact dupA on the gastric mucosa histology and IL-8 gastric levels. Colonization with strains that had the intact dupA was negatively associated with gastric carcinoma (p=0.001, OR=0.32, 95% CI=0.16-0.66). The presence of dupA was also associated with an increased degree of antral mucosa inflammation (p=0.01) and with decreased corpus atrophy (p<0.01) as well as with increased gastric mucosa IL-8 levels (p=0.04). In conclusion, the infection with a H. pylori strain containing the dupA without the stop codon polymorphisms is associated with a lower risk of development of gastric carcinoma in Brazilian subjects.

Role of Corpus Gastritis and cagA-Positive Helicobacter pylori Infection in Reflux Esophagitis

ABSTRACT Considering that the role of Helicobacter pylori infection in gastroesophageal reflux and reflux esophagitis (GERD) is still controversial and that the role of virulence markers of the bacterium has not been evaluated in most studies of GERD, we investigated the association among H. pylori infection with cagA-positive and -negative strains, corpus gastritis, and GERD in a large group of patients by controlling for confounding factors. We studied prospectively 281 consecutive adult patients: 93 with GERD and 188 controls. H. pylori infection status was diagnosed by culture, by the preformed urease test, with a carbolfuchsin-stained smear, and by histology. The cagA status was determined by PCR of H. pylori isolates and gastric biopsy specimens. H. pylori infection was diagnosed in 191 (68.0%) of 281 patients. Among the 93 patients with GERD, 84 presented with mild or moderate esophagitis and 9 presented with severe esophagitis. In the multivariate analysis, the age of the patients and the degree of oxyntic gastritis were associated with GERD. Among the strains isolated from patients with GERD and from the control group, 24.4 and 66.9%, respectively, were positive for cagA (P < 0.001). Compared to infection with cagA-negative strains, infection with cagA-positive H. pylori strains was associated with a more intense gastritis in the corpus (P = 0.001). cagA status (odds ratio [OR] = 0.16, 95% confidence interval [CI] = 0.07 to 0.40), gastritis of the corpus (OR = 0.69, 95% CI = 0.48 to 0.99), and age (OR = 1.04, 95% CI = 1.01 to 1.07) were associated with GERD. In conclusion, the study provides evidence supporting the independent protective roles of cagA-positive H. pylori strains and the degree of corpus gastritis against GERD.

Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency

Background:Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. Aim: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. Patients: Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied. Methods: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. Results: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) μmol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) μmol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment. Conclusions: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Apoptosis in Helicobacter pylori Gastritis is Related to cagA Status

Background:  Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa.

The interrelationship between Helicobacter pylori vacuolating cytotoxin and gastric carcinoma.

Objective:We aimed to determine whether cytotoxin-positive Helicobacter pylori strains are associated with gastric carcinoma.Methods:We studied 130 patients: 57 H. pylori-positive patients with gastric carcinoma, 53 H. pylori-positive patients without gastric carcinoma, and 20 H. pylori-negative subjects. The ability of H. pylori strains to produce vacuolating cytotoxin was tested in INT-407 and HeLa cells. The presence of antibodies to cytotoxin was investigated in blood serum from all subjects by immunoblotting. Fragments of the gastric mucosa from patients without gastric carcinoma and H. pylori-negative subjects were obtained for histopathological study.Results:Considering the results as a whole, 40 (70.2%) patients with and 22 (41.5%) without gastric carcinoma were colonized by cytotoxin-positive strains. Antibodies against cytotoxin were not observed in the serum from 17 (29.8%) gastric carcinoma patients and from 31 (58.5%) patients without gastric carcinoma. H. pylori strains isolated from these patients did not produce cytotoxin in vitro. In regard to cytotoxin positivity, a significant difference was observed between patients with and without gastric carcinoma (p= 0.004; odds ratio [OR]: 3.3; 95% confidence interval [CI]: 1.4–7.9). Higher scores of mononuclear (p= 0.0001) and polymorphonuclear (p= 0.000003) cells were observed in the antral mucosa from H. pylori-positive patients without gastric carcinoma infected by cytotoxin-positive strains than in those harboring cytotoxin-negative strains.Conclusion:Cytotoxin-producing H. pylori strains were more frequently observed in patients with gastric carcinoma and this aspect emphasizes the role of cytotoxin in the genesis of the tumor.