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

Chromoscopy-Guided Endomicroscopy Increases the Diagnostic Yield of Intraepithelial Neoplasia in Ulcerative Colitis

Background & Aims: Because of the large number of biopsy specimens, surveillance colonoscopy in ulcerative colitis (UC) is currently time consuming and significant flat lesions still may be missed. In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a randomized controlled trial. Methods: A total of 161 patients with long-term UC in clinical remission were randomized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy. Eight patients were excluded because of insufficient bowel preparation. In the conventional colonoscopic group (n = 73), random biopsy examinations and targeted bio…

Long-term Efficacy and Safety of Endoscopic Resection for Patients With Mucosal Adenocarcinoma of the Esophagus

Background & Aims Barrett's esophagus–associated high-grade dysplasia is commonly treated by endoscopy. However, most guidelines offer no recommendations for endoscopic treatment of mucosal adenocarcinoma of the esophagus (mAC). We investigated the efficacy and safety of endoscopic resection in a large series of patients with mAC. Methods We collected data from 1000 consecutive patients (mean age, 69.1 ± 10.7 years; 861 men) with mAC (481 with short-segment and 519 with long-segment Barrett's esophagus) who presented at a tertiary care center from October 1996 to September 2010. Patients with low-grade and high-grade dysplasia and submucosal or more advanced cancer were excluded. All patien…

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

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies

Abstract Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. …

Review article: in vivo imaging by endocytoscopy

Aliment Pharmacol Ther 2011; 33: 1183–1193 Summary Background  Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 μm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer. Aim  To systematically review the feasibility and diagnostic yield of EC for in vivo diagnosis of diseases. Methods  A systematic search of the literature on diagnostic interventions in the gastrointestinal tract u…

Confocal Laser Endomicroscopy for In Vivo Diagnosis of Early Squamous Cell Carcinoma in the Esophagus

Background & Aims: Confocal laser endomicroscopy has been shown to allow direct histologic imaging of gastrointestinal tumors in vivo. This study was designed to assess the potential of endomicroscopy for predicting histology in vivo during routine endoscopy in patients with early squamous cell cancer. Methods: Twenty-one consecutive patients with suspected early squamous cell cancer who had been referred for endoscopic therapy to a tertiary-care academic medical center were included in this prospective study. After staining with 0.5% Lugol's solution and injection of 500 mg fluorescein sodium, unstained mucosal areas were examined using confocal imaging. Images of each scanned lesion were …

Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking.The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients.Between September 1996 and September 2002, 667 patients with …

Mo1521 Endomicroscopy: Interobserver Agreement and Accuracy in Prediction of Intraepithelial Neoplasia in the Upper and Lower GI-Tract

Confocal laser endomicroscopy.

A miniaturized confocal microscope was developed that could be integrated in the distal tip of a conventional colonoscope. With this technique, denoted confocal endomicroscopy, subsurface analysis of the gut mucosa and in-vivo histology during ongoing endoscopy are possible in full resolution by point scanning laser analysis. The diagnostic spectrum of confocal endomicroscopy is expanding from screening and surveillance for colorectal cancer to Barrett's esophagus, Helicobacter pylori-associated gastritis, and gastric cancer. The new detailed images seen with confocal laser endomicroscopy allow a unique look on cellular structures at and below the surface of the gut. This review describes t…

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 …

European guidelines for quality assurance in colorectal cancer screening and diagnosis: Overview and introduction to the full Supplement publication

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recomme…

Diagnosing early Barrett’s neoplasia and oesophageal squamous cell neoplasia by bioimpedance spectroscopy in human tissue

Background: Detection of early oesophageal cancer in surrounding normal tissue can be challenging, but detection is essential to determine the subsequent treatment. Dysplastic tissue can be detected by using electrical impedance spectroscopy (EIS). Objective: The aim of the present study was to evaluate the feasibility and value of EIS in the diagnosis of oesophageal neoplasia. Methods: This prospective ex-vivo study included 23 patients with early oesophageal cancer (17 with Barrett’s cancer and six with early squamous cell cancer). Immediately after endoscopic resection, the electrical properties of the resected specimens were investigated using a pencil probe (5 mm in diameter, frequency…

Conclusions from the histological diagnosis of low-grade intraepithelial neoplasia in Barrett's oesophagus.

It is well known that low-grade intraepithelial neoplasia (LGIN) in Barrett's oesophagus (BE) might progress to high-grade intraepithelial neoplasia (HGIN) or carcinoma. Since accurate diagnosis of LGIN is difficult, general pathologists are frequently uncertain about the diagnosis of LGIN and its follow-up risks. The purpose of this study was to analyse the divergence between the diagnoses of general and specialized gastrointestinal pathologists.Fifty consecutive patients with a previous diagnosis of LGIN in BE, made by a general pathologist, were included in our study. The histopathological slides of every patient were reassessed in a blinded fashion by two specialized gastrointestinal (G…

Endoscopic assessment and grading of Barrett's esophagus using magnification endoscopy and narrow-band imaging: accuracy and interobserver agreement of different classification systems

Background: Three different classification systems for the evaluation of Barrett's esophagus (BE) using magnification endoscopy (ME) and narrow-band imaging (NBI) have been proposed. Until now, no comparative and external evaluation of these systems in a clinical-like situation has been performed. Objective: To compare and validate these 3 classification systems. Design: Prospective validation study. Setting: Tertiary-care referral center. Nine endoscopists with different levels of expertise from Europe and Japan participated as assessors. Patients: Thirty-two patients with long-segment BE. Interventions: From a group of 209 standardized prospective recordings collected on BE by using …

Extracranial metastasizing solitary fibrous tumors (SFT) of meninges: Histopathological features of a case with long-term follow-up

Extrapleural solitary fibrous tumors are uncommon mesenchymal neoplasms frequently observed in middle-aged adults and are classified, according to the WHO classification of soft tissue tumors, as part of the hemangiopericytoma tumor group. However, these two entities remain separated in the WHO classification of tumors of the central nervous system. In fact, meningeal solitary fibrous tumors are believed to be benign lesion and only in a minority of cases local relapses have been described, although detailed survival clinical studies on solitary fibrous tumors of meninges are rare. In contrast to hemangiopericytoma, which frequently shows distant extracranial metastases, such an event is ex…

Accuracy of staging in early oesophageal cancer using high resolution endoscopy and high resolution endosonography: a comparative, prospective, and blinded trial

The increasing use of endoscopic resection for curative treatment of early oesophageal cancers requires accurate staging before therapy. In a prospective blinded trial, we compared staging of early oesophageal carcinoma using high resolution endoscopy (HR-E) with staging using high resolution endosonography (HR-EUS).A total of 100 patients (89 men, 11 women; mean age 63.9 (10.8) years (range 31-91)) with a suspicion of early oesophageal adenocarcinoma (n = 81) or squamous cell carcinoma (n = 19) were enrolled in the study. After endoscopic staging with high resolution video endoscopy by two experienced endoscopists, HR-EUS was performed by an experienced endosonographer who was blinded to t…

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 …

Evidence for PTGER4, PSCA and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma

Contains fulltext : 235640.pdf (Publisher’s version ) (Closed access) Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analys…

In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease.

Background/Aims Histopathology is essential in the diagnostic workup of most liver diseases. However, biopsy sampling might carry risks, is subject to sampling error, and does not provide dynamic tissue imaging. Therefore a newly developed miniaturised confocal probe was evaluated for in vivo microscopic imaging in rodent models of human liver diseases. Methods The handheld laparoscopy probe used a 488nm single line laser for fluorophore excitation. Optical slice thickness was 7μm, lateral resolution 0.7μm. Imaging depth was 0–250μm below the tissue surface. Imaging using different fluorescent staining protocols was performed in healthy mice, IFNγ- and IL-12-induced hepatitis, after bile du…

Evidence for PTGER4 ,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome …

VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer.

Inflammation drives expression of VEGFR2, which is expressed on and drives growth of tumor cells in colitis-associated cancer.

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…

Comparison of methylene blue-directed biopsies and four-quadrant biopsies in the detection of high-grade intraepithelial neoplasia and early cancer in Barrett's oesophagus

Background. Barrett’s oesophagus embodies the risk of malignant transformation. High-grade intraepithelial neoplasia and early cancer in Barrett’s oesophagus are often discrete or macroscopically occult lesions and show a patchy distribution and therefore, directed biopsies in combination with four-quadrant random biopsies are the gold standard for surveillance. Aims. The aim of this prospective study was to compare methylene blue staining and random biopsies in patients with early Barrett’s neoplasia. Patients and methods. Eighty-six patients (mean age 65 ± 8 years) with histologically proven but macroscopically in evident high-grade intraepithelial neoplasia (n = 17) or early cancer in Ba…

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…

Long-term results of endoscopic resection in early gastric cancer: the Western experience.

Top of pageAbstract OBJECTIVES:  In the West, neither acute nor long-term results of endoscopic resection (ER) for early gastric cancer (EGC) have been reported in large studies. The aim of this study was to prospectively evaluate the efficacy and safety of ER in patients with EGC in a long-term follow-up (FU). METHODS:  From May 1995 to October 2004, 179 patients were referred to our department for endoscopic therapy (ET) of gastric cancer (GC). Of these, 43 patients had intramucosal GC with a diameter of up to 30 mm and underwent ER with curative intent. All patients underwent a strict FU protocol at regular intervals. RESULTS:  Of the 43 patients, 42 fulfilled our low-risk criteria for E…

Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo

Background & Aims: Aconfocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo. The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer. Methods: Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination. Furthermore, 42 patients underwent colonoscopy with this system using fluorescein sodium. Standardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens. Confocal images were graded accordin…

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

Contains fulltext : 215282.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(O…

The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central E…

Curative endoscopic resection of early esophageal adenocarcinomas (Barrett's cancer).

Background In view of the increasing incidence of adenocarcinoma in Barrett's esophagus and the mortality and high morbidity rates associated with surgical therapy for this condition, safe and effective but less invasive methods of treatment are needed. Objective To evaluate efficacy and safety of endoscopic resection in these patients. Design Single-center prospective study. Setting Teaching hospital, conducted between October 1996 and September 2003. Patients A total of 100 consecutive patients (mean age, 62.1 ± 10.9 years; range, 31–86 years) with low-risk adenocarcinoma of the esophagus (macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion without invasion…

Endoscopic Resection of Superficial Esophageal Squamous-Cell Carcinomas: Western Experience

Objectives Endoscopic resection of esophageal squamous-cell neoplasia with curative intent appears to be an alternative treatment to radical surgery when the malignant neoplasia is intraepithelial or limited to the mucosal layer, since the risk for lymph-node metastases is very low. In contrast to Japan, there has so far been only limited experience in Europe and the United States with endoscopic resection in such cases. In the present observational study, we report on the largest prospective series so far in Western countries of patients with early squamous-cell cancer or carcinoma in situ, who were treated using endoscopic resection therapy. Methods Between December 1997 and November 2001…

In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy.

Background & Aims: Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy. Here, we have applied this technique to the in vivo diagnosis of Barrett's epithelium and associated neoplasia. Methods: Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus. Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed. In vivo histology was compared with the histologic specimens. All digitally stored images were re-assessed by a b…

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic…