Regulation of apoptosis is impaired in atrophic gastritis associated with gastric cancer.

BACKGROUND: Gastric premalignant conditions, atrophic gastritis (AG) and intestinal metaplasia (IM) are characterized by an increase of proliferation and a reduction of apoptosis in epithelial cells. The epithelial cell kinetics in AG and IM in gastric mucosa adjacent to gastric cancer is still unclear. The aim of this study was to evaluate the epithelial cell turnover and expression of proliferation and apoptosis-related genes in gastric cancer (GC) and adjacent mucosa with atrophic gastritis or intestinal metaplasia (AG/IM GC+), as well as in atrophic gastritis or intestinal metaplasia mucosa of patients without GC (AG/IM GC-) and in control biopsy samples of non-transformed gastric mucosa (Control). METHODS: We selected 58 patients (M: F = 34:24; age range 20-84 years, median 61.06 years) with 4 well defined histological conditions: 20 controls with histological finding of non-transformed gastric mucosa, 20 patients with AG or IM (AG/IM GC-), and 18 patients with intestinal type gastric adenocarcinoma (GC) and AG or IM in the adjacent mucosa (3 cm from the macroscopic tumour margin, AG/IM GC+). We performed an immunohistochemical staining of Ki67 and TUNEL and quantitative RT-PCR to determine the expression of PCNA and Bax/Bcl-2. RESULTS: The immunohistochemical expression of Ki67 and TUNEL in AG/IM GC- was significantly increased compared to not transformed gastric mucosa (p < 0.0001) but not compared to AG/IM in gastric mucosa adjacent to GC. Levels of Bcl-2 were reduced in GC and AG/IM GC- compared to controls as well as in AG/IM GC- compared to AG/IM in mucosa adjacent to GC+ (p < 0.05). Proliferation and apoptosis markers did not correlate with H.pylori status in our study population. CONCLUSIONS: In AG/IM associated with GC, no significant changes in the epithelial cell turnover were detected. Decreased Bcl-2 gene expression signified atrophic gastritis and IM in presence of cancer, as well as intestinal type gastric adenocarcinoma.

Bacterial load and degree of gastric mucosal inflammation in Helicobacter pylori infection.

Helicobacter pylori induces an inflammatory immune response in the gastric mucosa. The degree of gastric mucosal inflammation and its topographic distribution are key factors in the diversity of H. pylori-related complications. Here we summarize substantial evidence reported in the literature concerning the impact of H. pylori density on gastric inflammation, the development of severe complications, and its relation to H. pylori suppression therapy. Most studies demonstrate a significant correlation between H. pylori density and the grade of acute and chronic inflammation, taking into account the limitations of each method for density assessment. Overall, high bacterial loads are associated with increased acute mucosal damage and long-term changes in the gastric mucosa. The influence of H. pylori density reduction on the improvement of gastric mucosal changes was observed in studies using 'clearance' therapies. Mucosal agents provoke a significant, but not persistent, reduction in gastritis activity. Treatments suppressing the density and virulence of H. pylori could become strategies to prevent H. pylori-associated disease in the future.

Helicobacter pylori and other gastric bacteria.

The discovery of Helicobacter pylori opened a new field for extensive research on the interactions of this bacterium with the gastric mucosa in the past decades. Basic principles of infection, virulence factors, and treatment options have been identified and recognized. New questions have emerged concerning possible interactions of H. pylori with other bacteria in the human stomach. Herein we discuss hallmark findings in relation to H. pylori infection and the new evidence on other bacteria in the human stomach. Probiotic bacteria seem to interfere with colonizing H. pylori bacteria and thus influence the inflammatory response of the gastric mucosa to H. pylori infection.

CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients.

Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence.

Impact of the angulus biopsy for the detection of gastric preneoplastic conditions and gastric cancer risk assessment.

BACKGROUND: Gastric atrophy and intestinal metaplasia (IM) are preneoplastic conditions in the development of gastric cancer. Histopathological assessment is based on the updated Sydney system and superordinate staging systems, operative link on gastritis assessment (OLGA) and operative link on gastritis assessment using IM (OLGIM), all requiring a biopsy from the incisura angularis (angulus). AIM: To determine the value of the angulus biopsy for the detection of preneoplastic conditions and cancer risk evaluation using OLGA and OLGIM prospectively. METHODS: Biopsies from antrum (2), angulus (1) and corpus (2) were obtained from 213 patients (age 19-94 years, median 54 years, female to male ratio 138:75) undergoing upper endoscopy. Histological assessment according to the updated Sydney system, OLGA and OLGIM staging was performed by gastrointestinal pathologists. Statistical analysis used exact confidence limits for dichotomous variables and repeated measurement analysis of variance. RESULTS: 8% of the cases with atrophic gastritis and 3% with IM (17 vs 6/213) would have been missed without the angulus biopsy. More patients were diagnosed with a preneoplastic condition when the angulus biopsy was considered (13.1%, CI 8.9% to 18.4%), but the grade of atrophy, if present at both sides, did not vary significantly in angulus and antrum. OLGA and OLGIM scores dropped significantly when recalculated without the angulus (difference in means±SD 0.131±0.402 and 0.075±0.313, respectively). The impact on the identification of high-risk stages is limited. CONCLUSIONS: The angulus biopsy adds to the detection of mild gastric atrophy in particular. It allows identifying a small additional number of patients with high-risk gastritis.

[Acute abdomen in a patient with ANCA-associated vasculitis]. / Akutes Abdomen bei ANCA-Assoziierter Vaskulitis.

HISTORY AND FINDINGS: A 49-year-old man complained of increasing pain in the lower left abdomen. Three weeks previously joint pain had developed, and in the last 7 days the patient had noted a cutaneous rash at the lower legs. Within three days after admission a paralytic ileus developed, progressed and culminated in a small bowel perforation. In the 60 cm ileum specimen as well as in the skin lesions there was marked intra- und perivascular infiltration with neutrophil granulocytes and focal necrosis, but no granuloma. DIAGNOSIS, TREATMENT AND COURSE: As the proteinase 3 subtype of antineutrophil cytoplasmic antibodies (ANCA) was positive ANCA-associated vasculitis with gastrointestinal, cutaneous and kidney involvement was diagnosed. After initiation of cytostatic treatment with methylprednisolone boli und cyclophosphamide the patient's condition improved. The post-operative course was uneventful. CONCLUSION: ANCA-associated vasculitis rarely presents with severe gastrointestinal complications. The disease represents an interdisciplinary challenge because of its variable clinical presentation and the possibly lethal outcome if not adequately treated.