A genome-engineered tool set for Drosophila TGF-β/BMP signaling studies.

Ligands of the TGF-β/BMP superfamily are crucially involved in the regulation of growth, patterning and organogenesis and can act as long-range morphogens. Essential for understanding TGF-β/BMP signaling dynamics and regulation are tools that allow monitoring and manipulating pathway components at physiological expression levels and endogenous spatiotemporal patterns. We used genome engineering to generate a comprehensive library of endogenously epitope- or fluorescent-tagged versions of receptors, co-receptors, transcription factors and key feedback regulators of the Drosophila BMP and Activin signaling pathways.

Safety of endoscopist-guided sedation in a low-risk collective.

Introduction:  Worldwide, gastrointestinal endoscopies are predominantly performed under sedation. National and international guidelines and recommendations contain very different specifications for the use of sedation in gastrointestinal endoscopy. These differences come from specific requirements for staffing during endoscopy.

Dichotomous cis-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling.

Retrograde bone morphogenetic protein (BMP) signaling at the Drosophila neuromuscular junction (NMJ) has served as a paradigm to study TGF-β-dependent synaptic function and maturation. Yet, how retrograde BMP signaling transcriptionally regulates these functions remains unresolved. Here, we uncover a gene network, enriched for neurotransmission-related genes, that is controlled by retrograde BMP signaling in motor neurons through two Smad-binding cis-regulatory motifs, the BMP-activating (BMP-AE) and silencer (BMP-SE) elements.

eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.

Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability.

Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression.

Hybrid APC in Combination With Resection for the Endoscopic Treatment of Neoplastic Barrett's Esophagus: A Prospective, Multicenter Study.

Introduction: The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation.

Methods: Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.

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

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.

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.

Infiltration Depth is the Most Relevant Risk Factor for Overall Metastases in Early Esophageal Adenocarcinoma.

Background: Research in early esophageal adenocarcinoma focused on prediction of lymph node metastases in order to stratify patients for endoscopic treatment instead of esophagectomy. Although distant metastases were described in rates of up to 13% of patients within a follow-up of 3 years, their prediction has been neglected so far.

Methods: In a secondary analysis, a cohort of 217 patients (53 T1a and 164 T1b) treated by esophagectomy was analyzed for histopathological risk factors.

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

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.

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

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.

The overall metastatic rate in early esophageal adenocarcinoma: long-time follow-up of surgically treated patients.

The overall metastatic potential of surgically treated early esophageal adenocarcinoma has not been studied in detail. This paper therefore assessed lymph node metastases at surgery, loco regional and distant metastases, in order to assess the metastatic potential of early esophageal adenocarcinoma. Two hundred and seventeen patients (53 T1a, 164 T1b; median follow-ups 87 and 75 months, 187 males) diagnosed with early esophageal adenocarcinoma and treated with esophagectomy in our tertiary center's database between July 2000 and December 2015 were included.

Non-thermal ablation of non-neoplastic Barrett's esophagus with the novel EndoRotor® resection device.

Background: International guidelines suggest endoscopic resection for all patients with low-risk mucosal cancer. Ultimately, it is essential to treat the remaining Barrett's esophagus as part of the treatment. Different thermal ablative therapies have been implemented to effect this treatment.

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

Objectives: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size.

Designs: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months).

The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

Background: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD).

Aim: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies.

Methods: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS.

Endoscopic resection for patients with mucosal adenocarcinoma of the esophagus.

Due to its rapidly increasing incidence in the last decade, esophageal adenocarcinoma has been attracting widespread interest among gastroenterologists all over the world. Advanced adenocarcinomas arising from intestinal metaplasia in the esophagus (Barrett's esophagus, BE) are associated with a poor prognosis when esophagectomy is required. In addition to high mortality rates, there is a significant morbidity rate among patients who undergo surgery.

Portal vein leiomyosarcoma: a case report and review of the literature.

Background: Leiomyosarcoma of vascular smooth muscle is a very rare entity. A fair number of cases of vascular leiomyosarcomas have been reported, and the vast majority of these tumors arose from the inferior vena cava.

Case Presentation: We report the case of a 71-year-old female patient who presented with recurrent upper abdominal pain.

[Safety of sedation during gastroscopy and colonoscopy in low-risk patients - results of a retrospective subgroup analysis of a registry study including over 170 000 endoscopies].

Introduction: Administering sedation is an established standard in gastrointestinal endoscopy, particularly in situations in which sedation is used to make the examination more comfortable for the patient (e. g., during preventive check-up examinations).

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

Background: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors.

ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286).

Background: Recent randomized controlled trials comparing neoadjuvant chemoradiation plus surgery or perioperative chemotherapy plus surgery with surgery alone showed significant survival benefits for combined modality treatment of patients with localized esophageal adenocarcinoma. However, head-to-head comparisons of neoadjuvant chemoradiation and perioperative chemotherapy applying contemporary treatment protocols are lacking. The present trial was initiated to obtain valid information whether neoadjuvant chemoradiation or perioperative chemotherapy yields better survival in the treatment of localized esophageal adenocarcinoma.