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ZusammenfassungÖsophagusmotilitätsstörungen sind Erkrankungen, bei denen es aufgrund einer Veränderung der neuromuskulären Strukturen zu Fehlfunktionen des Schluckakts kommt. Das Leitsymptom ist daher die Dysphagie für feste und/oder flüssige Speisen, häufig begleitet von Symptomen wie Thoraxschmerz, Regurgitation, Sodbrennen, und Gewichtsverlust. Die Ösophagusmanometrie ist der Goldstandard in der Diagnostik. Endoskopie und Radiologie dienen dem Ausschluss entzündlicher oder maligner Veränderungen.Durch die Einführung der hochauflösenden Ösophagusmanometrie (HRM) hat sich die Diagnostik der Ösophagusmotilitätsstörungen verbessert und mit der Chicago-Klassifikation zu einer neuen Einteilung geführt, die im letzten Jahrzehnt mehrfach modifiziert wurde, zuletzt 2020 mit der Chicago-Klassifikation v4.0. Verglichen mit der Vorversion v3.0 finden sich einige wichtige Änderungen, die anhand der im klinischen Alltag wichtigsten Ösophagusmotilitätsstörungen vorgestellt werden.

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.Ösophagusmotilitätsstörungen sind Erkrankungen, bei denen es aufgrund einer Veränderung der neuromuskulären Strukturen zu Fehlfunktionen des Schluckakts kommt. Das Leitsymptom ist daher die Dysphagie für feste und/oder flüssige Speisen, häufig begleitet von Symptomen wie Thoraxschmerz, Regurgitation, Sodbrennen und Gewichtsverlust. Die Ösophagusmanometrie ist der Goldstandard in der Diagnostik. Endoskopie und Radiologie dienen dem Ausschluss entzündlicher oder maligner Veränderungen.Durch die Einführung der hochauflösenden Ösophagusmanometrie (HRM) hat sich die Diagnostik der Ösophagusmotilitätsstörungen verbessert und mit der Chicago-Klassifikation zu einer neuen Einteilung geführt, die im letzten Jahrzehnt mehrfach modifiziert wurde, zuletzt 2021 mit der Chicago-Klassifikation v4.0. Verglichen mit der Vorversion v3.0 finden sich einige wichtige Änderungen, die anhand der im klinischen Alltag wichtigsten Ösophagusmotilitätsstörungen vorgestellt werden.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.Ösophagusmotilitätsstörungen sind Erkrankungen, bei denen es aufgrund einer Veränderung der neuromuskulären Strukturen zu Fehlfunktionen des Schluckakts kommt. Das Leitsymptom ist daher die Dysphagie für feste und/oder flüssige Speisen, häufig begleitet von Symptomen wie Thoraxschmerz, Regurgitation, Sodbrennen, und Gewichtsverlust. Die Ösophagusmanometrie ist der Goldstandard in der Diagnostik. Endoskopie und Radiologie dienen dem Ausschluss entzündlicher oder maligner Veränderungen.Durch die Einführung der hochauflösenden Ösophagusmanometrie (HRM) hat sich die Diagnostik der Ösophagusmotilitätsstörungen verbessert und mit der Chicago-Klassifikation zu einer neuen Einteilung geführt, die im letzten Jahrzehnt mehrfach modifiziert wurde, zuletzt 2020 mit der Chicago-Klassifikation v4.0. Verglichen mit der Vorversion v3.0 finden sich einige wichtige Änderungen, die anhand der im klinischen Alltag wichtigsten Ösophagusmotilitätsstörungen vorgestellt werden.

Die vollstandige Resektion von Tumorgewebe und erfolgreiche Rekonstruktion der Kontinuitat des Magen-Darm-Trakts sind in der onkologischen Viszeralchirurgie von essenzieller Bedeutung fur das postoperative Outcome. Neuerungen und Weiterentwicklungen in der intraoperativen Bildgebung ermoglichen die Visualisierung zuvor nur schwer beurteilbarer Parameter, wie der Gewebeperfusion und der Lymphdrainagewege. Dies erlaubt eine direkte Optimierung des operativen Verfahrens und kann somit zur Reduktion von Komplikationen und zur Erhohung der Patientensicherheit beitragen. Eine bereits in vielen Fachgebieten etablierte Methode der Echtzeitbildgebung ist das Fluoreszenz-Imaging mittels Indozyaningrun (ICG-FI). In der Viszeralchirurgie wird es aktuell besonders zur Perfusionsbeurteilung gastrointestinaler Anastomosen und zum „Lymphknoten-Mapping“ eingesetzt. Jedoch werden in ersten Untersuchungen auch weitere mogliche Anwendungsgebiete beschrieben, beispielsweise die Detektion von Lebermetastasen und Peritonealkarzinosen im Rahmen von Staging-Untersuchungen oder der zytoreduktiven Chirurgie. Eine weitere vielversprechende Methode ist das Hyperspektral-Imaging (HSI), welches sich aktuell noch in einer experimentellen Phase befindet, zukunftig aber ein wichtiges Instrument zur noninvasiven Perfusionsbeurteilung und Gewebedifferenzierung darstellen konnte. Im vorliegenden Beitrag wird ein Uberblick uber die aktuellen Anwendungsgebiete neuer intraoperativer Imaging-Verfahren gegeben und auf neue Moglichkeiten und Perspektiven der modernen „image-guided surgery“ hingewiesen.

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. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 × 10−04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10−02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10−03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10−02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10−03) and WHR and BE/EA risk variants (P = 2 × 10−02). Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. Impact: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

Das lokal fortgeschrittene, irresektable (nichtmetastasierte) und grenzwertig resektable Pankreaskarzinom stellt eine therapeutische Herausforderung dar. Zur lokalen Behandlung in diesen Situationen stehen verschiedene minimal-invasive lokal ablative Verfahren zur Verfugung. Welche interventionellen Verfahren und Anwendungsmoglichkeiten liegen derzeit beim Pankreaskarzinom vor und welche onkologischen Ergebnisse konnten hiermit bisher erzielt werden? Auswertung von Reviews und Studien. Die Selektion der Literatur erfolgte auf der Basis von Recherchen in PubMed und der Cochrane-Library. Ausgewertet wurden Reviews/Metaanalysen und Originalarbeiten vorwiegend aus dem Zeitraum von 2013 bis 2018. Einzelfallberichte wurden bei der Erstellung der Ubersichtsarbeit nicht berucksichtigt. Die lokal ablativen Verfahren werden mit unterschiedlichen Energieformen durchgefuhrt und sind mit spezifischen Vor- und Nachteilen verbunden. Sie mussen individuell auf den Patienten und die spezifische Situation angepasst werden. Die nichtinvasive Thermoablation mit hochintensivem fokussiertem Ultraschall (HIFU) dient vor allem der palliativen Schmerzlinderung. Mikrowellenablation (MWA) und Radiofrequenzablation (RFA) werden meist zur thermischen Nekrose solider Tumoren angewendet. Die irreversible Elektroporation (IRE) ermoglicht eine selektive Zerstorung von Tumorzellen und kann in der Nahe sensibler Strukturen vorgenommen werden. Sie wird sowohl zur primaren Tumorkontrolle als auch zur Akzentuierung der Tumorgrenzen wahrend der Resektion eingesetzt. Mit lokal ablativen Verfahren kann bei Patienten mit nichtresektablen Pankreaskarzinomen eine Verbesserung der Lebensqualitat und moglicherweise der Prognose erzielt werden, wenngleich der letzte Aspekt in Ermangelung einer fundierten Datenlage kritisch zu betrachten ist.

Purpose In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. Methods Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. Results MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13–3.37, P = 0.63) and 1.44 (95% CI 0.66–3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14–0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89–1.58, P = 0.26). Conclusion Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

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. 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. Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p

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 patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0–7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6–187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2–116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3–28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0–9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8–85.6) and 53.5% (50.9–56.1), respectively (OR 0.25, 95% CI 0.08–0.75, p = 0.001). Conclusions Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

During the course of a malignant disease, the tumor needs to be classified repeatedly in order to facilitate decision-making in treatment and to estimate patients prognosis; however, a wrong classification of tumors can occur in different stages of the disease course with tremendous consequences for the affected patients. This review discusses the possible misclassifications which can occur in patients with esophageal cancer or adenocarcinoma of the esophagogastric junction (EGJ), along with the consequences.

BACKGROUND: Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. METHODS: This was a cross-sectional retrospective study. Achalasia patients from tertiary centres in the Czech Republic (n = 163), Germany (n = 114), Greece (n = 70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal–Wallis test was used for the genotype-phenotype analysis. RESULTS: A total of 347 achalasia patients (type I – 89, II – 210, III – 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p = 0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). CONCLUSION: The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.

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 analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

Background Patients with Barrett's esophagus (BE) may experience psychological burden from living with a chronic medical condition, which has been identified as the most important risk factor for esophageal adenocarcinoma. The aim of this study was to estimate rates of depression and anxiety in a large sample of patients with BE. Methods A total of 794 patients with endoscopically and histologically confirmed diagnosis of BE completed validated screening instruments for depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). Screening rates in the study sample were compared to general population estimates. Multivariable regression analyses were used to model associations between outcome variables and respondents' sociodemographic characteristics, BE-related symptom load and incidence of inpatient treatment due to BE in the last 12 months. Results Rates of positive screens were 14.2% for depression and 9.9% for anxiety. For several age by sex subgroups, rates of depression and anxiety were about three to five times higher in the study sample than in the general population. BE-related reflux and pain symptoms showed strong associations with higher levels of depressive and anxiety symptoms, while the effect of treatment was small. Conclusion Study results indicate that a relevant proportion of patients with BE is at an increased risk for depression and anxiety, compared to general population controls. Lacking information on patients' disease characteristics limited generalizability of results.

The technique of hybrid esophagectomy with systematic 2‑field lymphadenectomy for esophageal cancer showed a significant reduction in postoperative morbidity in a recently published prospective randomized study. This video publication presents the abdominothoracic hybrid procedure with (i) laparoscopic gastrolysis and ischemic conditioning of the stomach and (ii) 2-stage transthoracic esophagectomy with gastric pull-up, intrathoracic gastric tube formation and anastomosis. Intraoperative hyperspectral imaging (HSI) during the thoracic part of the operation is used for identification of the ideally perfused anastomotic region.

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 8q24 at rs2585176 (P = 1.09 x 10(-09)). On chromosome 5p13 we found cis-eQTL effects with an up-regulation of PTGER4 expression in GC risk allele carrier (P = 9.27 x 10(-11)). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 x 10(-47)). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 x 10(-09)). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms.

Any surgical procedure develops a stress situation for the patient, which can modulate the individual outcome. At present, there is only limited information about stress response in colorectal resections by laparoscopic compared to conventional surgery. Therefore, our objectives were the feasibility and the investigation of stress biomarkers including copeptin and steroid hormones before, during and after colorectal surgery.Eleven patients underwent minimally invasive and ten patients conventionally open colorectal surgery. Blood samples were collected before, during and 24 h after surgery and copeptin, NT-proBNP, cortisol, cortisone, interleukin-6 and glucose were analyzed.Both, minimally invasive and conventional-open colorectal surgery caused a fast but heterogeneous response of stress biomarkers. However, the postoperative decrease of cortisol, cortisone and glucose differed between both groups. The stress biomarkers decreased faster down to baseline after minimally invasive surgery, while in open surgery cortisol, cortisone and glucose did not return to baseline within 24 h after operation.We show in this feasibility study for the first time an increase of copeptin in combination with glucocorticoids as stress biomarkers by open surgery compared to minimally invasive procedures in patients undergoing colorectal surgery. Exceeding an individual threshold of 'stress burden' may have unfavorable effects on the long-time clinical outcome.

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 association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5?0⁻⁸) and novel candidate loci (5?0⁻⁸ ≤ P ≤ 5?0⁻⁵). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcₒmbinₑd = 3.16?0⁻⁷ and rs1540, Pcₒmbinₑd = 4.16?0⁻⁶) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. CA extern

BACKGROUND AND AIM Although an eight-residue insertion in HLA-DQβ1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype-phenotype (G×P) analysis to gain further insights into the etiology of achalasia. METHODS We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls). For the G×P analysis, we stratified the patients into HLA-DQβ1 insertion carriers and noncarriers. RESULTS Our data show that patients are more often affected by viral infections before achalasia onset (P

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 conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence.

Background Locally advanced unresectable (nonmetastatic) and borderline resectable pancreatic carcinomas represent a therapeutic challenge. Several minimally invasive local ablative techniques are available for local treatment in these situations. Objective Which interventional techniques and application options are currently available for pancreatic carcinoma and which oncological results could be achieved so far? Material and methods An analysis of reviews and studies was carried out. The selection of literature was based on searches in PubMed and the Cochrane library. The studies analyzed were reviews, meta-analyses and original articles mainly from the period between 2013 and 2018. Single case reports were not included in this review. Results Local ablative techniques are performed with various forms of energy and are associated with specific advantages and disadvantages. They have to be individually tailored to the specific patient and situation. Noninvasive thermal ablation with high-intensity focused ultrasound (HIFU) is primarily used for palliative pain relief. Solid tumors are the main indication for thermal necrosis with microwave ablation (MWA) and radiofrequency ablation (RFA). The use of irreversible electroporation (IRE) enables a selective destruction of tumor cells and can be performed in the vicinity of sensitive structures. This technique is applied for primary tumor control and also for accentuation of tumor margins during resection. Conclusion With local ablative techniques an improvement in the quality of life and possibly the prognosis can be achieved in patients with unresectable pancreatic cancer; however, the latter aspect has to be viewed with caution due to a current lack of well-founded data.

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(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

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 conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence.