Prävalenz von Alarm-, dyspeptischen und Reflux-Symptomen bei Patienten mit Adenokarzinom des ösophagogastralen Übergangs und Magenkarzinom

Molecular diagnostics in gastric cancer.

Despite recent advances in individualised targeted therapy, gastric cancer remains one of the most challenging diseases in gastrointestinal oncology. Modern imaging techniques using endoscopic filter devices and in vivo molecular imaging are designed to enable early detection of the cancer and surveillance of patients at risk. Molecular characterisation of the tumour itself as well as of the surrounding inflammatory environment is more sophisticated in the view of tailored therapies and individual prognostic assessment. The broad application of high throughput techniques for the description of genome wide patterns of structural (copy number aberrations, single nucleotide polymorphisms, meth…

Magenkarzinom auf dem Boden einer Autoimmungastritis: eine Fall-Kontroll-Studie aus dem staR (gastric cancer research)-Konsortium

Mismatch Reparatur Defizienz, Chemotherapie und Überleben bei resektablem Magenkarzinom: Eine Beobachtungsstudie der deutschen Zentren des staR-Projekts und eine Metaanalyse

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research

Objectives Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. Methods Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. Results Histological assessment of gastric mucosa was available for 572/759 GC …

Sorafenib in Patients with Hepatocellular Carcinoma-Results of the Observational INSIGHT Study.

Abstract Purpose: Sorafenib is the only currently approved systemic therapy for advanced hepatocellular carcinoma (HCC). We aimed to evaluate the safety and efficacy of sorafenib therapy in patients with HCC under real-life conditions regarding patient, tumor characteristics, and any adverse events at study entry and at follow-up visits every 2 to 4 months. Experimental Design: The current INSIGHT study is a noninterventional, prospective, multicenter, observational study performed in 124 sites across Austria and Germany between 2008 and 2014. Results: Median overall survival and time to progression (RECIST) were found to be dependent on baseline Barcelona Clinic Liver Cancer (BCLC) tumor s…

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis …

ESOPHAGEAL “OUTLET PATCHY VESICLES”: ENDOSCOPIC, MAGNIFICATION ENDOSCOPY, HISTOLOGIC AND ELECTRONMICROSCOPIC DESCRIPTION OF NEW LESIONS AT THE GASTROESOOPHAGEAL JUNCTION

The Barrett‐associated variants at GDF 7 and TBX 5 also increase esophageal adenocarcinoma risk

Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and …

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

Abstract Background Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. Methods Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>…

Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis

Background & Aims A number of double, triple, and quadruple therapies have been proposed as first-line empiric treatments for Helicobacter pylori infection. However, knowledge of their worldwide and regional comparative efficacy is lacking. We examined the comparative effectiveness of all empirically used first-line regimens tested against standard triple treatment using a network meta-analysis of published randomized controlled trials. Methods Data extracted from eligible randomized controlled trials were entered into a Bayesian network meta-analysis to investigate the comparative efficacy of H pylori infection empiric first-line regimens and to explore their effectiveness rank order. The …

Tumor-associated autoantibody signature for the early detection of gastric cancer

Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signal…

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer.

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time po…

How do international gastric cancer prevention guidelines influence clinical practice globally?

Clinical guidelines recommend particular approaches, including 'screen-and-treat' strategy for Helicobacter pylori, to prevent gastric cancer. However, little of this is implemented in clinical practice. The aim of the study was to identify barriers to implementation of international guidelines. A web-based questionnaire distributed globally to specialists in the field. Altogether 886 responses from 75 countries were received. Of the responders, 570 (64%) were men of mean age 47 years. There were 606 gastroenterologists and 65 epidemiologists among the responders. Altogether, 79.8% of the responders disagreed that the burden of gastric cancer is a diminishing problem. 'Screen-and-treat' str…

Supportive evidence for FOXP 1 , BARX 1 , and FOXF 1 as genetic risk loci for the development of esophageal adenocarcinoma

The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could repl…

Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density.

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactiv…

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

Background and Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.&#x0D; Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire.&#x0D; Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 ca…

Markers for gastric cancer premalignant lesions: where do we go?

Only a small proportion of patients infected with &lt;i&gt;Helicobacter pylori&lt;/i&gt; develop gastric cancer during their lifetime. At the same time, this type of cancer remains an important cause of mortality globally. The current interventional strategies have not been successful in decreasing the global burden of the disease; therefore, biomarkers for the identification of the individuals at high risk as well as those in the early stage of the disease is of high importance. In addition, predicting the point of no return for the development of the malignancy is of particular interest; whether atrophy, intestinal or spasmolytic polypeptide-expressing metaplasia, or some of their subtype…

Final Analysis of Overall Survival Per Subgroups of Hcc Patients in the Prospective, Non-Interventional Insight Study Treated with Sorafenib

ABSTRACT Aim: INSIGHT is a prospective, non-interventional study, conducted in Germany and Austria in pts with hepatocellular carcinoma HCC. The objectives of this study are the evaluation of safety and efficacy under practice conditions in both hospitals and private practices. Enrollment into INSIGHT is not restricted to a particular tumor stage. Methods: This final analysis evaluated overall survival and safety data incluling relevant subgroups. All patients with HCC were observed for the duration of their sorafenib therapy. In addition to baseline data the performance status, tumor status (clinical and/or radiological), and overall survival time are documented. Documentation of adverse e…

Neurotransmitter in Pankreasnerven: Ein Beitrag zur Schmerzgenese bei chronischer Pankreatitis

Ursache und Pathogenese des langjahrigen Schmerzsyndromes bei chronischer Pankreatitis sind nach wie vor ungeklart. Ein neues Konzept der Schmerzgenese bei chronischer Pankreatitis, namlich spezifische Veranderungen an den Pankreasnerven, wurde vor kurzem erstmals beschrieben (1). Es handelt sich hierbei neben einer Vermehrung und Grosenzunahme von extrinsischen und intrinsischen neuralen Strukturen im Pankreas um eine Zerstorung des perineuralen Bindegewebes, welches als wirksame Schutzbarriere gegenuber humoralen und cellularen Einflussen im gesunden menschlichen Pankreas fungiert.

Interim Analysis of Overall Survival Per Subgroups in the Prospective, Non-Interventional Insight Study in Patients with Hepatocellular Carcinoma Treated with Sorafenib

ABSTRACT Background The efficacy of Sorafenib in patients (pts) with hepatocellular carcinoma (HCC) has been proven in randomized, controlled trials. INSIGHT is a prospective, non-interventional study, conducted in Germany and Austria in pts with HCC. The objectives of this study are the evaluation of safety and efficacy under practice conditions in both hospitals and private practices. Enrollment into INSIGHT is not restricted to a particular tumor stage. Recruitment into the study is ongoing. Methods The second interim analysis (data cut-off 23 FEB 2012) evaluated overall survival and safety data in relevant subgroups. All patients with HCC were observed for the duration of their sorafeni…

S3-Leitlinie „Magenkarzinom” -