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  • Oxford University Press (OUP)  (17)
  • 1
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    O129 CLASSIFICATION OF BARRETT’S CARCINOMA SPECIMENS BY HYPERSPECTRAL IMAGING (HSI)
    Oxford University Press (OUP) ; 2019
    In:  Diseases of the Esophagus Vol. 32, No. Supplement_2 ( 2019-11-23)
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    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 32, No. Supplement_2 ( 2019-11-23)
    Abstract: Hyperspectral imaging (HSI) technology combines imaging with spectroscopy and can be used for the classification of malignant and non-malignant cells. Thereby HSI combined with artificial intelligent algorithms can be used to predict tumor cells in in Barrett’s carcinoma specimens. Methods HSI imaging records light between the visual and near-infrared light (500-1000nm). For a first feasibility study, this technique was used to discriminate between squamous epithelium and esophageal adenocarcinoma and 45 specimens from Barrett’s carcinoma patients were recorded. In 22 of the 45 investigated specimens contained also squamous epithelium. The specimens were fixed routinely after resection in paraformaldehyde, were sliced to 3μm, and were stained by haematoxylin and eosin (HE). A non-parametric supervised classification learning algorithm (K-nearest neighbours (k-NN)) was used for discrimination. Results Barrett’s adenocarcinoma cells were recorded by HSI in all 45 investigated cases. Squamous epithelium and Barrett’s adenocarcinoma cells displayed differences in the absorbance between the wave lengths of 500 to 700 nm. For both, the squamous epithelium and the Barrett’s adenocarcinoma cells, the intra group variances of the investigated specimens were quite low. 333,275 and 74,000 spectra could be measured from Barrett’s adenocarcinoma and from squamous epithelium, respectively. Specificity, sensitivity and precision with a k-NN (k=5) classifier were 0.74, 0.92 and 0.94 for the presence of Barrett’s adenocarcinoma cells. Conclusions HE-stained squamous epithelium and Barrett’s adenocarcinoma cells showed specific spectral alterations, when measured by HSI. These characteristics could be used in the future to develop a computer-assisted algorithm to discriminate semi-automated for tumor cells Barrett’s carcinoma specimens, which will help to foster decision-making support in histopathological diagnosis.
    Type of Medium: Online Resource
    ISSN: 1442-2050
    URL: Article
    DOI: 10.1093/dote/doz092.129
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 2
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    428. CHARACTERIZATION OF CD82/KAI1 IN ESOPHAGEAL ADENOCARCINOMA
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. Supplement_2 ( 2022-09-24)
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    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: The incidence of esophageal adencocarcinoma (EAC) has increased in last decades. Regardless to improved perioperative chemotherapies and surgical approaches, the prognosis for EAC in advanced stages is poor. CD82 is a tumor suppressor gene, and its downregulation correlates with invasive growth, metastases formation and advanced clinical stages. CD82 might influence the Wnt/ß-catenin signaling pathway. We used an in vitro Barrett’s esophagus cell culture model, represented by esophageal squamous cell epithelium (EPC1, EPC2), metaplasia (CP-A), dysplasia (CP-B) and esophageal adenocarcinoma (OE33, OE19, SKGT4, FLO1). Antisense LNA Oligonucleotides (GapmeRs, Qiagen) were used to achieve a transient knockdown of CD82 in OE33 and OE19 cells. mRNA and proteins were analyzed by q-RT-PCR and western blot analyses, respectively. A fluorescence antibody specific to CD82 was used for flow cytometry analysis. Proliferation assay, colony formation assay and boyden chamber assay were performed after CD82-knockdown to further analyze cell proliferation, cell growth and survival, colony forming and cell migration. CD82 was expressed in all investigated cell lines by flow cytometry with a significant overexpression in OE19 and FLO1 cells. A stable downregulation of CD82 was achieved in OE33 and OE19 cells. Proliferation assays showed a significantly higher proliferation rate at 72 hours after CD82-knockdown in OE33 cells. A significantly higher mRNA expression of vimentin was observed after CD82-knockdown in OE33. Colony formation assay showed a significantly higher colony count after CD82-knockdown in both cell lines. Cell migration was increased after CD82-downregulated in OE33 and OE19 cells. CD82 might influence the expression of mesenchymal marker proteins, cell migration abilities and the process of colony forming and thus enhance the metastatic potential of OE33 and OE19 cells. Low expression of CD82 could alter metastasis and cancer progression but further molecular characterizations are needed to elucidate the impact on carcinogenesis of EAC.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doac051.428
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    PS02.044: A BARRETT’S CELL CULTURE MODEL, SHOWING AN INCREASED ACID TOLERABILITY OF ESOPHAGEAL ADENOCARCINOMA CELLS
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 132-132
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 132-132
    Abstract: Inflammation is a common in esophageal adenocarcinoma (EAC). The response of EAC to common chemotherapeutic regimes is relatively low and the 5-years-survival is poor. The influence of acidic reflux on the viability of esophageal adenocarcinoma cells is unknown. Methods We investigated the influence of acidified medium conditions (pH3; pH3.5; pH4) in a Barrett's cell culture model, using six cell lines representing the Barrett's sequence from normal esophageal epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B) and EAC (OE33 and OE19) for their tolerability against an acid pulse of 15 and 30 min as well as expression profile of the Nrf2-Keap1-signalling pathway and their downstream targets. Results The Barrett's sequence was characterized by an increase of acid tolerability in the more advanced cells of this sequence. The squamous epithelium cell line EPC1 has shown the highest susceptibility with a decrease of 75% of cell viability, when treated with pH4 medium for 15min, while dysplastic and EAC cells had shown only a decrease of 10–25%. The lowest susceptibility was observed in the EAC cell line OE33, which had also 90% living cell in pH3 medium after 15min and had almost 30% living cells after 30min, when all other investigated cell lines showed no more living cells. Additionally, treatment with acidified medium was accompanied with an increase of the Nrf2 target gene hemeoxygensae-1. Conclusion We could show an increased tolerability against acidified medium (pH3) in cells representing advanced Barrett's esophagus stages, accompanied by an activation of Keap1-Nrf2-signalling pathway. However, acidic reflux may influence inflammation and chemo-sensitivity of the EAC. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.PS02.044
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 4
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    420. IDENTIFICATION AND CLASSIFICATION OF TUMOR CELLS IN PATIENTS WITH BARRETT’S CARCINOMA BY HYPERSPECTRAL IMAGING (HSI)
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. Supplement_2 ( 2022-09-24)
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: Hyperspectral imaging (HSI), as recently applied in medicine, is a novel technology combining imaging with spectroscopy. It might be used to identify, classify and discriminate malignant and non-malignant cells of histopathologic specimens. HSI allows the determination of a spectrum between the visual and near-infrared light (500-1000 nm). After surgical resection, specimens (n = 96) of Barrett’s cancer were fixed in 4% formaldehyde and slices were conducted (3 μm), which were stained with hematoxylin and eosin (HE). Differences in the absorbance of squamous epithelium and esophageal adenocarcinoma (EAC) cells were determined at eosin’s and hematoxylin’s maximal absorption of 530 nm and 590 nm. A classification algorithm, which combines a multilayer perceptron (MLP) with a Gaussian filter and data reduction based on principal component analysis (PCA) was used for discrimination. For the first time in literature, we were able to analyze esophageal adenocarcinoma, tumor stroma and squamous epithelium cells by HSI. For both, the squamous epithelium and the esophageal adenocarcinoma cells, the intragroup variances were quite low. A set of 20 specimens was used in a testing phase, which showed MLP by using reflectance data to provide the best results. Leave-one-patient-out-cross validation for all 96 specimens showed an accuracy of 77% with a sensitivity of 87% and a specificity of 72% for EAC determination and visualization. Squamous epithelium and EAC cells show specific spectral alterations due to their HE-staining, when measured by HSI. However, the training algorithms need further validation to foster a semi-automatic decision-making process in histopathological tumor cell identification.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doac051.420
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
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    427. CHARACTERIZATION OF THE CYTOSKELETON-ASSOCIATED PROTEIN 4 (CKAP4) IN A BARRETT’S ESOPHAGUS CELL CULTURE MODEL
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. Supplement_2 ( 2022-09-24)
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: While the incidence of EAC is rapidly increasing, its prognosis remains poor, with a five-year survival rate of 20%. Consequently, the discovery of new molecular targets for an efficient characterization of EAC patients is necessary. CKAP4 has been attributed to be increased in various cancer entities and has a role in tumorigenesis. However, its role in EAC development and progression is widely unknown. In a Barrett’s esophagus, in vitro cell culture model of BE and EAC, CKAP4 expression levels were verified with qPCR, western blot and FACS analysis. In OE33 and OE19 cells a knockdown of CKAP4-expression was done by siRNA for 48 h and 72 h. In siCKAP4 transfected cells FACS (apoptosis), western blot analysis, colony forming assay (CFA), transmigration, adhesion and proliferation assays, were performed. Using western blot, the impact of CKAP4-knockdown on the phosphorylation of Akt, MAP-Kinase, GSK3ß and ß-Catenin was investigated. Furthermore, DKK1-, Ki67- and p21-mRNA-expression was analyzed in siCKAP4 cells using qPCR. CKAP4 was present in all cell lines of the Barrett’s sequence (squamous epithelium, metaplasia, dysplasia, and EAC). CKAP4 surface expression was significantly increased in OE33, OE19 and Flo-1 cells. The phosphorylation of Akt was decreased in OE19 cells only, whereas the phosphorylation of MAP-kinase was reduced in OE33 cells, suggesting a role of CKAP4 in tumor-associated proliferation. This was confirmed by decreased colonies in CFA in siCKAP4 cells. FACS analysis showed a significant increase in the amount of apoptotic cells after siCKAP4 transfection. SiCKAP4 led to an increased expression of adhesion molecules, suggesting an impact of CKAP4 in cell adhesion. The role of CKAP4 is barely investigated in EAC at this time. Acting as a Dickkopf-1 (DKK1) receptor, the DKK1-CKAP4-axis might promote cell proliferation independently to the Wnt-pathway. Based on our current results, it can be assumed, that CKAP4 is important for EAC cell growth, proliferation and cell adhesion. Nevertheless, further characterization of CKAP4 is necessary, particularly focusing on the CKAP4-DKK1-axis to provide more evidence for its contribution in EAC development.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doac051.427
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    Hyperspectral imaging as a new optical method for the measurement of gastric conduit perfusion
    Oxford University Press (OUP) ; 2019
    In:  Diseases of the Esophagus Vol. 32, No. 10 ( 2019-12-13), p. 1-1
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 32, No. 10 ( 2019-12-13), p. 1-1
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doz046
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 7
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    PS02.057: INDUCTION OF APOPTOSIS IN ESOPHAGEAL ADENOCARCINOMA CELLS BY CURCUMIN
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 136-137
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 136-137
    Abstract: Curcumin naturally occurring in curry powder from Curcuma longa is an anti-inflammatory and anti-proliferative agent. It represses NFκB activation and induces apoptosis in cancer cells. Because, inflammation favours the onset of an intestinal metaplasia in esophageal squamous epithelial cells and esophageal carcinoma cells, a reduction of such processes may contribute to establish a stable disease and/or sensitization for chemotherapeutic approaches. Methods Curcumin receptivity was investigated in metaplastic (CP-A), dysplastic (CP-B), adenocarcinoma (OE19, OE33), and esophageal fibroblast (FFE3) cell lines, which were treated with 10 or 25 μM Curcumin for 48h or 72h. Response to Curcumin was measured by proliferation assays as well as by induction of apoptosis and Akt activation by western blot analyses. Results The EAC cell lines OE33 and OE19 show a decrease of proliferation with raising curcumin concentration with an IC50 of 9.6 and 14.8 μM, respectively. While the metaplastic and dysplastic cell lines showed a comparable IC50 of 7.7 and 11.6 μM to the EAC cell lines, the FEF3 cell showed a higher IC50 of approx. 20μM. The phosphorylation of Akt was decreased and apoptosis was induced, showing cleaved PARP, when treated with 25μM curcumin after 48h and 72h. Conclusion Metaplastic, dysplastic and EAC cells show a higher receptivity to curcumin than esophageal fibroblasts cells. This constrains the NFκB activation and its contribution in the manifestation of the Barrett's esophagus. The usage of curcumin to generate an anti-inflammatory microenvironment will potentially help to develop a stable disease or to reverse the development of the Barrett's esophagus. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.PS02.057
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 8
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    415. A WEBCAST FOR THE EDUCATION AND INFORMATION OF PATIENTS WITH BARRETT’S ESOPHAGUS AND BARRETT’S CANCER
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. Supplement_2 ( 2022-09-24)
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    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: To provide expert knowledge to patients becomes more and more important, especially during the Sars-CoV-2 pandemics, where self-helping groups could not meet and on-site information events could not take place. We discovered a need due to patients’ uninformedness about diagnostic procedures, treatment options and advice for disease prevention or special nutrition and medications after the diagnosis of Barrett’s esophagus and Barrett’s cancer. A webpage was created, including a video streaming platform (https://webcast.barrett-initiative.de/). The events were performed live with the opportunity to ask questions via the chat function. Vimeo was used for the live streaming. Three to four lecturers were invited and one moderator organized the sequence of talks and questions. Additionally, the webpage is contains an encyclopedia, to explain disease related terms in a patient-orientated language. The invitation was done based on our nation-wide patient network based on genes for barrett’s (g4b) study https://www.barrett-konsortium.de/. Patients used a desktop computer (65%), mobile phones (28%), and tablets (7%) to join the video sessions. The lecture series was started with a kick-off event in September 2021 to give a bright overview about reflux, Barrett’s esophagus und Barrett’s cancer. Four special topic events were conducted, dealing with tumor biology, cancer prevention, diagnostics needed for the correct staging and how the diagnostic will guide the therapy by explaining the expertise review board, discussing operability and prehabilitation. The series will be continued by the endoscopic and surgical treatment options. There were 1,100 views to the webpage. While during the kick-off 204 patients were online, approx. 71 to 171 patients saw the following events during the live sessions. Based on the questions by our patients and the continuous participation at our livestream events, we discovered an urgent need to provide a platform to patients, where they can find disease specific information in a patients-oriented language. Therefore, all lectures were deposited to a media archive where they are available to patients. We implemented our webcast project as a growing platform to cover aspects from the disease development, to diagnosis, treatment, and follow-up care.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doac051.415
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 9
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    590. GERD AND BARRETT`S ESOPHAGUS IN BARIATRIC SURGERY
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. Supplement_2 ( 2022-09-24)
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    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. Supplement_2 ( 2022-09-24)
    Abstract: The role of preoperative Gastroscopy in obesity surgery in detecting a lot of abnormalities of Upper-GI such as GERD and BE`s has been already proved in our pervious study. The Development of GERD and BE`s after bariatric surgery still controversy in the bariatric surgery. The Aim of this study is to evaluate the development of GERD and BE`s in patients underwent bariatric surgery including LGB and LSG In our single center prospectively-established database of obese patients, who u nderwent bariatric surgery from 01/2012 to 12/2019, we retrospectively compare the preoperative endoscopic finding of patients with BE`s to these findings after 1-2 years and 3-5 years after the bariatric surgery. The regression of BE’s was defined based on the endoscopic findings as a 1 cm down grade of Prague classification circumferential (C) as well as maximum extent (M) or complete regression of BE’s, histologically as a conversion of intestinal metaplasia to squamous epithelium or conversion of dysplastic dysplasia to intestinal metaplasia Among 914 bariatric patients, we found 119 patients (13%) with BE`s. A control gastroscopy could be performed in 74 BE`s Patients. 37 patients received a control gastroscopy after 1-2 years and 47 patient after 3-5 years. The surgical procedure was the only significant factor for the development of GERD and BE`s after bariatric surgery (P & lt; 0.05). Progression of GERD after LGB was detected only in one patient (4.2%, n=54) and in 10 patients (50%, n=10) after LSG in patients. Furthermore, the progression of BE`s after LGB in 4 patient (7.4%, n=54) and in 6 patients (30%, n=20) after LSG Laparoscopic gastric bypass should be considered in obese patients with GERD or BE`s. Therefore, detecting of GERD and BE`s prior to bariatric surgery may has an obvious impact on decision making regarding the suitable surgical bariatric procedure
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doac051.590
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 10
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    O128 TGF-BETA1 AND TGF-BETA2 MEDIATED EPITHELIAL-MESENCHYMAL TRANSITION IN ESOPHAGEAL ADENOCARCINOMA CELLS
    Oxford University Press (OUP) ; 2019
    In:  Diseases of the Esophagus Vol. 32, No. Supplement_2 ( 2019-11-23)
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 32, No. Supplement_2 ( 2019-11-23)
    Abstract: he esophageal adenocarcinoma (EAC) is characterized by an early lymphogenic dissemination and a poor prognosis. The tumor biology and the impact of autocrine, paracrine and endocrine mediators are involved in these mechanisms. For dissemination, the tumor cells need to escape the solid tumor and invade into new target structures. This mechanism is described as epitheliale-mesenchymal transition (EMT), which could be initiated by TGF-beta Methods Two proliferation and motility of the esophageal adenocarcinoma cell lines (OE33, OE19) were analyzed after TGF-beta1 and TGF-beta2 treatment. EMT marker gene expressions (e.g. vimentin) were assessed by qRT-PCR. Results TGF-beta2 led to a deceased proliferation rate compared to untreated and TGF-beta1 treated cells in OE33 cells. In OE19 cells both, TGF-beta1 and TGF-beta2 treatment resulted in an increased proliferation compared to untreated cells. In OE33 cells the motility was affected by TGF-beta1 only, while in OE19 cells the motility was increased by TGF-beta1 and TGF-beta2 compared to untreated cells. The vimentin mRNA-expression in OE33 cells was increased by TGF-beta1 and TGF-beta2 (14.7-fold and 25.9-fold). However TGF-beta1 and TGF-beta2 only led to a moderate increase in the vimentin mRNA-expression (4.0-fold and 1.8-fold) in OE19 cells. Conclusion TGF-beta1 and TGF-beta2 induce EMT and cellular motility in a cell line specific pattern. The responsible intracellular signaling cascades addressed by TGF-beta1 and TGF-beta2 and their contribution for dissemination in EAC patients need to be investigated with full details.
    Type of Medium: Online Resource
    ISSN: 1442-2050
    URL: Article
    DOI: 10.1093/dote/doz092.128
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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