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.

[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

Assessment and monitoring of liver function by ¹³C-aminopyrine breath test after selective transarterial chemoembolisation of hepatocellular carcinoma.

BACKGROUND: Liver function and tumor staging are essential parameters for selection of treatment modalities in patients with hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is associated with a risk of deterioration of liver function. In clinical routine hepatic function in patients with liver cirrhosis is assessed by the Child-Pugh-classification. Dynamic breath tests allow the assessment of the hepatic functional mass and have the potential to give more accurate information on hepatic function periinterventionally. PATIENTS AND METHODS: A prospective clinical study was performed in 13 patients receiving a total of 18 TACE sessions. (13)C-aminopyrine breath test was performed the day before TACE, 2 days and 30 days after TACE and correlated with standard laboratory work-up of the patients. RESULTS: Fourteen TACE sessions were performed in Child A liver cirrhosis, 4 in Child B cirrhosis. All patients presented with impaired aminopyrine metabolism at baseline. No significant changes in the (13)C aminopyrine breath test following TACE were observed. Two patients treated in Child A cirrhosis decompensated to Child B, one of them recovered. No further decompensation was observed in patients treated in Child B cirrhosis. DISCUSSION AND CONCLUSION: Liver function assessment with (13)C-aminopyrine breath test and Child-Pugh-classification following TACE was discordant in a large proportion of patients. Whether a quantification of mitochondrial liver function in patients planned to undergo locoregional treatment of HCC in liver cirrhosis is helpful in the prediction of postprocedural liver decompensation needs to be addressed in larger prospective clinical trials.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

Host polymorphisms of immune regulatory genes as risk factors for gastric cancer.

The infection of the stomach with the gram-negative bacterium Helicobacter pylori is the main risk factor for the development of gastric cancer (GC). This led to the classification of this germ as "definite carcinogen" by the World Health Organization in 1994. The current model of gastric carcinogenesis is based on the interaction of multiple risk factors including virulence factors of the bacterium (e.g. CagA, VacA), environmental factors (diet, smoking) and host factors (gene polymorphisms). The complex interplay among these factors determines the clinical outcome of the infection leading to at least one of three major diseases in 1 out of 7 infected persons, namely ulcer disease, GC and "mucosa-associated lymphoid tissue" lymphoma in 15 %, 1% and 0.1% of all persons infected with H. pylori, respectively. Recently, an increasing number of genomic polymorphisms, mostly single nucleotide polymorphisms have been identified as risk factors for gastric cancer. Among them are genes encoding for cytokines, pattern recognition receptors, cell cycle-regulators, proteases, HLA-molecules, and enzymes for detoxification. In the last years it has become clear that an uniform "genomic risk pattern" for all GC patients does not exist. Most of these host factors are restricted either to the histological type (intestinal vs. diffuse), ethnical background (particularly Caucasian vs. Asian) and tumor localization (non-cardia vs. cardia cancer). Here, we review the current knowledge about the role of host factors for the gastric carcinogenesis focusing on immune-regulatory genes, in particular on the cytokine interleukin-1beta.

The combined presence of H pylori infection and gastro-oesophageal reflux disease leads to an up-regulation of CDX2 gene expression in antrum and cardia.

BACKGROUND: CDX2 is an epithelial transcription factor that regulates intestinal differentiation and is involved in the development of intestinal metaplasia (IM). AIM: To analyse the expression of CDX2 in the gastric mucosa in various locations and its relationship to Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD). METHODS: 69 patients with upper gastrointestinal symptoms were stratified into four groups according to their H pylori and GORD status. Patients without infection and without GORD were the reference group (H pylori(-)/GORD(-)). Biopsies from the antrum, corpus and cardia were assessed by histopathology according to the updated Sydney System. CDX2 transcription levels were determined by quantitative RT-PCR and immunohistochemistry. RESULTS: CDX2 gene expression was significantly up-regulated in antral and cardia mucosa of patients with both H pylori infection and GORD (26- and 100-fold, respectively; p<0.05), but remained unchanged in corpus mucosa. If only H pylori infection or GORD was present, CDX2 expression levels were 6- to 11-fold increased in the antrum, but without reaching statistical significance. CDX2 expression correlated positively with the degree of IM (p<0.01) and the degree of H pylori induced inflammation (p<0.05). Gene expression data were confirmed immunohistochemically by the detection of CDX2 in areas of IM and in focally distributed CDX2-expressing cells in non-metaplastic gastric mucosa. CONCLUSIONS: The combined presence of H pylori infection and GORD leads to an up-regulation of CDX2 gene expression in cardia and antral mucosa, but not in the corpus.

[S3-guideline "Helicobacter pylori and gastroduodenal ulcer disease"]. / S3-Leitlinie "Helicobacter pylori und gastroduodenale Ulkuskrankheit" der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS).

This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level and has also implemented grading criteria according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics and therapy were taken into account.

[Gastrointestinal neuroendocrine tumors]. / Neuroendokrine Tumoren des Gastrointestinaltraktes.

Two thirds of all neuroendocrine tumors (NET) are located in the gastroentero-pancreatic system. Depending on its localisation, each tumor presents a different histological pattern as well as different clinical symptoms and prognosis. Symptoms are usually due to the mass effects of the local tumor or tumor-related fibrosis. The classical "carcinoid-syndrome" with flush and diarrhea is seen in fewer than 10 %. Tests like chromogranin A (serum) or 5-hydroxyindolacetic acid (24h urine-collection) are indicators for the initial diagnosis of NET. Somatostatin-receptor scintigraphy is the most valuable imaging modality. In addition CT/MRI can be used for further topographical definition. Endoscopic techniques like the use of capsule endoscopy are being evaluated for the diagnosis of small intestinal NETs. The only curative treatment of NET is still complete surgical resection. However, it can only be done in 20 %, depending on localization and local extension of the primary tumor. If the liver is involved local ablation techniques should be considered. The gold standard for medical treatment is the use of somatostatin analogs, although interferons show a comparable therapeutic potential. Traditional cytotoxic agents should only be used for poorly differentiated tumors refractory to other forms of treatment. New compounds that target different pathways at the intra- and intercellular level are under investigation. Supportive therapy should be considered for the control of symptoms.