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An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Background: Hyperspectral Imaging (HSI) is a reliable and safe imaging method for taking intraoperative perfusion measurements. This is the first study translating intraoperative HSI to an in vivo laparoscopic setting using a CE-certified HSI-system for minimally invasive surgery (HSI-MIS). We aim to compare it to an established HSI-system for open surgery (HSI-Open). Methods: Intraoperative HSI was done using the HSI-MIS and HSI-Open at the Region of Interest (ROI). 19 patients undergoing gastrointestinal resections were analyzed in this study. The HSI-MIS-acquired images were aligned with those from the HSI-Open, and spectra and parameter images were compared pixel-wise. We calculated the Mean Absolute Error (MAE) for Tissue Oxygen Saturation (StO2), Near-Infrared Perfusion Index (NIR-PI), Tissue Water Index (TWI), and Organ Hemoglobin Index (OHI), as well as the Root Mean Squared Error (RMSE) over the whole spectrum. Our analysis of parameters was optimized using partial least squares (PLS) regression. Two experienced surgeons carried out an additional color-change analysis, comparing the ROI images and deciding whether they provided the same (acceptable) or different visual information (rejected). Results: HSI and subsequent image registration was possible in 19 patients. MAE results for the original calculation were StO2 orig. 17.2% (± 7.7%), NIR-PIorig. 16.0 (± 9.5), TWIorig. 18.1 (± 7.9), OHIorig. 14.4 (± 4.5). For the PLS calculation, they were StO2 PLS 12.6% (± 5.2%), NIR-PIPLS 10.3 (± 6.0), TWIPLS 10.6 (± 5.1), and OHIPLS 11.6 (± 3.0). The RMSE between both systems was 0.14 (± 0.06). In the color-change analysis; both surgeons accepted more images generated using the PLS method. Conclusion: Intraoperative HSI-MIS is a new technology and holds great potential for future applications in surgery. Parameter deviations are attributable to technical differences and can be reduced by applying improved calculation methods. This study is an important step toward the clinical implementation of HSI for minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196). ∼75 x 10 6 SNP×SNP interactions were screened via hierarchical group lasso (glinternet) using BEACON GWAS data. The top ∼2000 interactions retained in each scan were prioritized using P values from single logistic models. Identical scans were repeated among males only (78%), with two independent GWAS datasets used for replication. In overall and male-specific primary replications, 11 of 187 and 20 of 191 interactions satisfied P<0.05, respectively. The strongest evidence for secondary replication was for rs17744726×rs3217992 among males, with consistent directionality across all cohorts (P meta =2.19×10 -8 ); rs3217992 "T" was associated with reduced risk only in individuals homozygous for rs17744726 "G". Rs3217992 maps to the CDKN2B 3'UTR and reportedly disrupts microRNA-mediated repression. Rs17744726 maps to an intronic enhancer region in BLK. Through in-silico prioritization and experimental validation, we identified a nearby proxy variant (rs4841556) as a functional modulator of enhancer activity. Enhancer-gene mapping and eQTLs implicated BLK and FAM167A as targets. The first systematic G×G investigation in BE/EAC, this study uncovers differential risk associations for CDKN2B variation by BLK genotype, suggesting novel biological dependency between two risk loci encoding key mediators of tumor suppression and inflammation., (Copyright © 2025. Published by Elsevier Inc.)

Purpose: HER2 inhibition represents a therapeutic approach with proven clinical efficacy in gastric cancer. However, resistance against HER2-directed therapeutics highlights the need for alternative approaches or drug combinations. Histone deacetylase inhibitors (HDACi) display a broad spectrum of antitumor properties, which may include effects on receptor tyrosine kinases., Materials and Methods: We analyzed the effects of the class I HDACi entinostat in a panel of HER2-amplified and non-amplified gastric adenocarcinoma cells in 2D cell culture as well as in tumor slice models ex vivo and in patient-derived xenografts in vivo. Effects on protein expression / signal transduction were evaluated by immunoblotting and quantitative RT-PCR., Results: HDAC inhibition reduced HER2 protein expression independently of initial HER2 expression levels. This was associated with the upregulation of the HER2-inhibiting microRNA miR-205. The downregulation of HER2 resulted in reduced AKT phosphorylation, apoptosis induction and antiproliferative effects, with particularly high efficiency in HER2-amplified gastric cancer cells. Inhibiting HER2 by a specific kinase inhibitor in gastric cancer cells with low basal HER2 expression led to HER2 upregulation. This was reversed by entinostat treatment and provided the basis for synergistic cell inhibition upon double treatment., Conclusion: We describe the downregulation of HER2 in gastric carcinoma cells upon HDACi treatment. Concomitantly, cells with high basal or treatment-induced HER2 expression showed most profound sensitivities towards HDACi. These findings may thus provide the basis for HDACi treatment as a therapeutic option (1) particularly valuable in HER2-amplified gastric cancer and (2) particularly useful in combination therapies with HER2 inhibitors.

Purpose: This study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer., Methods: A total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC)., Results: Ten years after recruitment, 0.16% (95%CI 0.11-0.26%) had esophageal cancer and 4.17% (95%CI 3.86-4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C., Conclusion: TyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification., (© 2024. The Author(s).)

Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease., Methods: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany., Results: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs., Conclusions: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Aurora kinase A (AURKA) plays a pivotal role in regulating cell mitosis and tumor progression. However, its prognostic significance across diverse cancer types remains relatively unexplored., Methods: We conducted a comprehensive analysis of AURKA expression in various cancers using data from The Cancer Genome Atlas, Genotype-Tissue Expression, and The Human Protein Atlas databases. Our investigation encompassed an exploration of the associations between AURKA expression and clinical characteristics, shedding light on potential functional roles of AURKA. Additionally, we delved into the relationship between AURKA and the tumor microenvironment. To substantiate the role of AURKA, we carried out in vitro experiments in esophageal adenocarcinoma (EAC), prostate cancer (PRAD), and pancreatic cancer (PAAD) cells., Results: Our analysis revealed that AURKA is prominently overexpressed in a majority of the cancer types under investigation. Elevated AURKA expression correlated closely with poorer prognosis and advanced tumor stages. AURKA was found to be associated with key pathways involved in the cell cycle and arachidonic acid metabolism. Moreover, AURKA expression exhibited significant correlations with immunoregulatory genes and immune cell profiles. Notably, in vitro experiments demonstrated that silencing AURKA expression resulted in reduced cell viability in EAC, PRAD, and PAAD cells, as well as a decrease in clone formation, cell cycle elongation, diminished cell invasion and reduced spheroid size in EAC cells (OE33 and OE19)., Conclusion: Our study elucidates the oncogenic role of AURKA and underscores its prognostic value across a spectrum of cancers, including EAC. These findings suggest that AURKA holds promise as a predictive biomarker for EAC and various other tumor types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Plum, Gockel and Thieme.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity., Methods: Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior., Results: One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: - 1079; 95% CI - 2157 to - 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life., Conclusions: Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed., Trial Registration: DRKS-ID: DRKS00020499 ; Registered 17 March 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following., Competing Interests: Bzgl. Nukleosid/Nukleotid-Analoga zur Behandlung der chronischen Hepatitis B: AT erhielt Beratungs- und Vortragshonorare sowie Forschungsförderung der Firma Gilead., (Thieme. All rights reserved.)

Introduction: Fluorescence angiography (FA) with indocyanine green (ICG) and hyperspectral imaging (HSI) are novel intraoperative visualization techniques in abdominal, vascular and transplant surgery. With the purpose of precision surgery, and in order to increase patient's safety, these new tools aim at reducing postoperative morbidity and mortality. This review discusses and highlights recent developments and the future potential of real-time imaging modalities., Methods: The underlying mechanisms of the novel imaging methods and their clinical impact are displayed in the context of avoiding anastomotic leaks, the most momentous complications in gastrointestinal surgery after oncologic resections., Results: While FA is associated with the admission of a fluorescence agent, HSI is contact-free and non-invasive. Both methods are able to record physiological tissue properties in real-time. Additionally, FA also measures dynamic phenomena. The techniques take a few seconds only and do not hamper the operative workflow considerably. With regard to a potential change of the surgical strategy, FA and HSI have an equal significance. Our own advancements reflect, in particular, the topics of data visualization and automated data analyses together with the implementation of artificial intelligence (AI) and minimalization of the current devices to install them into endoscopes, minimal-invasive and robot-guided surgery., Conclusion: There are a limited number of studies in the field of intraoperative imaging techniques. Whether precision surgery in the "high-tech" OR together with FA, HSI and robotics will result in more secure operative procedures to minimize the postoperative morbidity and mortality will have to be evaluated in future multicenter trials., Competing Interests: Hannes Köhler war bis August 2020 Mitarbeiter der Firma Diaspective Vision. Zurzeit ist er Beschäftigter der Universität Leipzig (ICCAS, Innovation Center Computer Assisted Surgery). Er erhält derzeit keine finanzielle Unterstützung der Firma, somit besteht zurzeit kein Interessenkonflikt. Alle weiteren Autoren geben an, zum gegenwärtigen Zeitpunkt ebenso keine Interessenkonflikte zu haben., (Thieme. All rights reserved.)

Purpose: WNT5A/ROR2 signaling pathway has been involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The purpose of this study was to determine the prognostic value of WNT5A expression in conjunction with the ROR2 expression in the same PDAC human tissues., Methods: We retrospectively analyzed by immunohistochemistry the WNT5A and ROR2 expression in117 paraffin-embedded PDAC specimens following surgical pancreatic resection. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate Cox regression models., Results: High ROR2 expression was detected in 65.8% (77/117) of PDAC tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation coefficiency demonstrated weak association between ROR2 and WNT5A expression in tumor (r=0.184; p=0.047), and no association in stroma (r=0.036; p=0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A expression were not., Conclusions: Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2 and WNT5A expression in our cohort, either alone or in subgroup analysis, underlines the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness - 8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness-8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Esophageal adenocarcinoma (EAC) is still associated with poor prognosis, despite modern multi-modal therapies. New molecular markers, which control cell cycle and promote lymph node metastases or tumor growth, may introduce novel target therapies. Dickkopf-1 (DKK1) is a secreted glycoprotein that blocks the oncogenic Wnt/β-catenin signaling and its aberrant expression has been observed in many malignancies, including EAC. In this study, we investigated the biological role of DKK1 in EAC. Analysis of DKK1 and active β-catenin expression in human esophageal tissues confirmed a simultaneous DKK1-overexpression together with aberrant activation of β-catenin signaling in EAC in comparison with Barrett's and healthy mucosa. To elucidate the molecular role of DKK1, the OE33 adenocarcinoma cells, which were found to overexpress DKK1, were subjected to functional and molecular assays following siRNA-mediated DKK1-knockdown. At the functional level, OE33 cell viability, proliferation, migration and invasion were significantly attenuated by the absence of DKK1. At the molecular level, neither DKK1-knockdown nor application of exogenous recombinant DKK1 were found to alter the baseline β-catenin signaling in OE33 cells. However, DKK1-knockdown significantly abrogated downstream Akt-phosphorylation. On the other hand, the Wnt-agonist, Wnt3a, restored the Akt-phorphorylation in the absence of DKK1, without, however, being able to further stimulate β-catenin transcription. These findings suggest that the β-catenin transcriptional activity in EAC is independent of Wnt3a/DKK1 site-of-action and define an oncogenic function for DKK1 in this type of malignancy via distinct activation of Akt-mediated intracellular pathways and independently of Wnt-axis inhibition. Taken together, DKK1 may present a novel therapeutic target in EAC., Competing Interests: None.