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

Author

Dighe, Shruti G, primary, Chen, Jianhong, additional, Yan, Li, additional, He, Qianchuan, additional, Gharahkhani, Puya, additional, Onstad, Lynn, additional, Levine, David M, additional, Palles, Claire, additional, Ye, Weimin, additional, Gammon, Marilie D, additional, Iyer, Prasad G, additional, Anderson, Lesley A, additional, Liu, Geoffrey, additional, Wu, Anna H, additional, Dai, James Y, additional, Chow, Wong-Ho, additional, Risch, Harvey A, additional, Lagergren, Jesper, additional, Shaheen, Nicholas J, additional, Bernstein, Leslie, additional, Corley, Douglas A, additional, Prenen, Hans, additional, deCaestecker, John, additional, MacDonald, David, additional, Moayyedi, Paul, additional, Barr, Hugh, additional, Love, Sharon B, additional, Chegwidden, Laura, additional, Attwood, Stephen, additional, Watson, Peter, additional, Harrison, Rebecca, additional, Ott, Katja, additional, Moebus, Susanne, additional, Venerito, Marino, additional, Lang, Hauke, additional, Mayershofer, Rupert, additional, Knapp, Michael, additional, Veits, Lothar, additional, Gerges, Christian, additional, Weismüller, Josef, additional, Gockel, Ines, additional, Vashist, Yogesh, additional, Nöthen, Markus M, additional, Izbicki, Jakob R, additional, Manner, Hendrik, additional, Neuhaus, Horst, additional, Rösch, Thomas, additional, Böhmer, Anne C, additional, Hölscher, Arnulf H, additional, Anders, Mario, additional, Pech, Oliver, additional, Schumacher, Brigitte, additional, Schmidt, Claudia, additional, Schmidt, Thomas, additional, Noder, Tania, additional, Lorenz, Dietmar, additional, Vieth, Michael, additional, May, Andrea, additional, Hess, Timo, additional, Kreuser, Nicole, additional, Becker, Jessica, additional, Ell, Christian, additional, Ambrosone, Christine B, additional, Moysich, Kirsten B, additional, MacGregor, Stuart, additional, Tomlinson, Ian, additional, Whiteman, David C, additional, Jankowski, Janusz, additional, Schumacher, Johannes, additional, Vaughan, Thomas L, additional, Madeleine, Margaret M, additional, Hardie, Laura J, additional, and Buas, Matthew F, additional

Published
2020
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102. Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma

Author

Dong, Jing, primary, Maj, Carlo, additional, Tsavachidis, Spiridon, additional, Ostrom, Quinn T., additional, Gharahkhani, Puya, additional, Anderson, Lesley A., additional, Wu, Anna H., additional, Ye, Weimin, additional, Bernstein, Leslie, additional, Borisov, Oleg, additional, Schröder, Julia, additional, Chow, Wong-Ho, additional, Gammon, Marilie D., additional, Liu, Geoffrey, additional, Caldas, Carlos, additional, Pharoah, Paul D., additional, Risch, Harvey A., additional, May, Andrea, additional, Gerges, Christian, additional, Anders, Mario, additional, Venerito, Marino, additional, Schmidt, Thomas, additional, Izbicki, Jakob R., additional, Hölscher, Arnulf H., additional, Schumacher, Brigitte, additional, Vashist, Yogesh, additional, Neuhaus, Horst, additional, Rösch, Thomas, additional, Knapp, Michael, additional, Krawitz, Peter, additional, Böhmer, Anne, additional, Iyer, Prasad G., additional, Reid, Brian J., additional, Lagergren, Jesper, additional, Shaheen, Nicholas J., additional, Corley, Douglas A., additional, Gockel, Ines, additional, Fitzgerald, Rebecca C., additional, Cook, Michael B., additional, Whiteman, David C., additional, Vaughan, Thomas L., additional, Schumacher, Johannes, additional, Thrift, Aaron P., additional, and Dong, Jing, additional

Published
2020
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105. Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies

Author

Böhmer, Anne C., primary, Hecker, Julian, additional, Schröder, Julia, additional, Gharahkhani, Puya, additional, May, Andrea, additional, Gerges, Christian, additional, Anders, Mario, additional, Becker, Jessica, additional, Hess, Timo, additional, Kreuser, Nicole, additional, Thieme, René, additional, Noder, Tania, additional, Venerito, Marino, additional, Veits, Lothar, additional, Schmidt, Thomas, additional, Fuchs, Claudia, additional, Izbicki, Jakob R., additional, Hölscher, Arnulf H., additional, Dietrich, Arne, additional, Moulla, Yusef, additional, Lyros, Orestis, additional, Lang, Hauke, additional, Lorenz, Dietmar, additional, Schumacher, Brigitte, additional, Mayershofer, Rupert, additional, Vashist, Yogesh, additional, Ott, Katja, additional, Vieth, Michael, additional, Weismüller, Josef, additional, Moebus, Susanne, additional, Knapp, Michael, additional, Neuhaus, Horst, additional, Rösch, Thomas, additional, Ell, Christian, additional, Nöthen, Markus M., additional, Whiteman, David C., additional, Tomlinson, Ian, additional, Jankowski, Janusz, additional, Fitzgerald, Rebecca C., additional, Palles, Claire, additional, Vaughan, Thomas L., additional, Gockel, Ines, additional, Thrift, Aaron P., additional, Fier, Heide, additional, and Schumacher, Johannes, additional

Published
2020
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111. Autorinnen und Autoren

Author

Bauer, Hartwig, primary, Bechstein, Wolf O., additional, Becker, Heinz, additional, Bollschweiler, Elfriede, additional, Bösing, Norbert M., additional, Branscheid, Detlev, additional, Cupisti, Kenko, additional, Diemel, Klaus D., additional, Dotzenrath, Cornelia, additional, Drücke, Daniel, additional, Ebener, Christoph, additional, Encke, Albrecht, additional, Fieguth, Hans-Gerd, additional, Franke, Claus, additional, Ghadimi, B. Michael, additional, Goretzki, Peter E., additional, Groß-Weege, Wilhelm, additional, Grund, Karl E., additional, Gutschow, Christian, additional, Hanisch, Ernst, additional, Hesterberg, Rudolf, additional, Heller, Klaus, additional, Hölscher, Arnulf H., additional, Hölscher, Moritz, additional, Holzer, Katharina, additional, Homann, Heinz H., additional, Hopt, Ulrich T., additional, Horeyseck, Günter, additional, Horstmann, Olaf, additional, Langer, Claus, additional, Langer, Stefan, additional, Lenhardt, Marcus, additional, Leister, Ingo, additional, Liersch, Torsten, additional, Lorf, Thomas, additional, Luther, Bernd L.P., additional, Markus, Bernd H., additional, Markus, Peter M., additional, Menger, Michael D., additional, Möslein, Gabriela, additional, Müller-Dornieden, Annegret, additional, Neugebauer, Edmund A.M., additional, Ohmann, Christian, additional, Olbrisch, Rolf R., additional, Post, Stefan, additional, Raffel, Andreas, additional, Riess, Hanno, additional, Ritter, Ralf-Gerhard, additional, Röher, Hans-Dietrich, additional, Röhrborn, Ansgar, additional, Sachs, Michael, additional, Schaudt, André, additional, Schlemminger, Rolf, additional, Schmidt, W. Ulrich, additional, Schmidt-Matthiesen, Andreas, additional, Schmitz-Rixen, Thomas, additional, Schneider, Paul M., additional, Schröder, Wolfgang, additional, Schulte, Klaus-Martin, additional, Schulze, Frank P., additional, Simanski, Christian J.P., additional, Simon, Dietmar, additional, Steinau, Hans Ulrich, additional, Steinsträsser, Lars, additional, Steitz, Heinrich Otto, additional, Thon, Klaus-Peter, additional, Ulsenheimer, Klaus, additional, Vallböhmer, Daniel, additional, Wagner, Roland, additional, Wahl, Robert A., additional, Weiner, Rudolf A., additional, and Wenisch, Hubertus C., additional

Published
2006
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112. No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study

Author

Dong, Jing, Gharahkhani, Puya, Chow, Wong-Ho, Gammon, Marilie D, Liu, Geoffrey, Caldas, Carlos, Wu, Anna H, Ye, Weimin, Onstad, Lynn, Anderson, Lesley A, Bernstein, Leslie, Pharoah, Paul D, Risch, Harvey A, Corley, Douglas A, Fitzgerald, Rebecca C, Stomach And Esophageal Cancer Study Consortium, Iyer, Prasad G, Reid, Brian J, Lagergren, Jesper, Shaheen, Nicholas J, Vaughan, Thomas L, MacGregor, Stuart, Love, Sharon, Palles, Claire, Tomlinson, Ian, Gockel, Ines, May, Andrea, Gerges, Christian, Anders, Mario, Böhmer, Anne C, Becker, Jessica, Kreuser, Nicole, Thieme, Rene, Noder, Tania, Venerito, Marino, Veits, Lothar, Schmidt, Thomas, Schmidt, Claudia, Izbicki, Jakob R, Hölscher, Arnulf H, Lang, Hauke, Lorenz, Dietmar, Schumacher, Brigitte, Mayershofer, Rupert, Vashist, Yogesh, Ott, Katja, Vieth, Michael, Weismüller, Josef, Nöthen, Markus M, Moebus, Susanne, Knapp, Michael, Peters, Wilbert HM, Neuhaus, Horst, Rösch, Thomas, Ell, Christian, Jankowski, Janusz, Schumacher, Johannes, Neale, Rachel E, Whiteman, David C, Thrift, Aaron P, Caldas, Carlos [0000-0003-3547-1489], Pharoah, Paul [0000-0001-8494-732X], Fitzgerald, Rebecca [0000-0002-3434-3568], and Apollo - University of Cambridge Repository

Subjects
Esophageal Cancer, Etiology, Risk Factors, Chemoprevention, BEACON
Abstract

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.

Published
2019
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113. Anastomotic techniques and associated morbidity in total minimally invasive transthoracic esophagectomy

Author

Schröder, Wolfgang, Raptis, Dimitri A, Schmidt, Henner M, Gisbertz, Suzanne S, Moons, Johnny, Asti, Emanuele, Luyer, Misha D P, Hölscher, Arnulf H, Schneider, Paul M, van Berge Henegouwen, Mark I, Nafteux, Philippe, Nilsson, Magnus, Räsanen, Jari, Palazzo, Francesco, Mercer, Stuart, Bonavina, Luigi, Nieuwenhuijzen, Grard A P, Wijjnhoven, Bas P L, Pattyn, Piet, Grimminger, Peter P, Bruns, Christiane J, Gutschow, Christian A, University of Zurich, and Gutschow, Christian A

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2019

118. Ösophaguskarzinom 1,2

Author

Schneider, Paul M., primary, Metzger, Ralf, additional, Baldus, Stephan E., additional, Warnecke-Eberz, Ute, additional, Bruns, Christiane J., additional, Brabender, Jan, additional, Stöltzing, Oliver, additional, and Hölscher, Arnulf H., additional

Published
2002
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132. Endoscopic Treatment of Transesophageal Echocardiography-Induced Esophageal Perforation

Author

Herbold, Till, Chon, Seung-Hun, Grimminger, Peter, Maus, Martin K H, Schmidt, Henner, Fuchs, Hans, Brinkmann, Sebastian, Bludau, Marc, Gutschow, Christian, Schröder, Wolfgang, Hölscher, Arnulf H, Leers, Jessica M, University of Zurich, and Herbold, Till

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2018
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134. 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

Author

Schröder, Julia, primary, Schüller, Vitalia, additional, May, Andrea, additional, Gerges, Christian, additional, Anders, Mario, additional, Becker, Jessica, additional, Hess, Timo, additional, Kreuser, Nicole, additional, Thieme, René, additional, Ludwig, Kerstin U., additional, Noder, Tania, additional, Venerito, Marino, additional, Veits, Lothar, additional, Schmidt, Thomas, additional, Fuchs, Claudia, additional, Izbicki, Jakob R., additional, Hölscher, Arnulf H., additional, Dakkak, Dani, additional, Jansen-Winkeln, Boris, additional, Moulla, Yusef, additional, Lyros, Orestis, additional, Niebisch, Stefan, additional, Mehdorn, Matthias, additional, Lang, Hauke, additional, Lorenz, Dietmar, additional, Schumacher, Brigitte, additional, Mayershofer, Rupert, additional, Vashist, Yogesh, additional, Ott, Katja, additional, Vieth, Michael, additional, Weismüller, Josef, additional, Mangold, Elisabeth, additional, Nöthen, Markus M., additional, Moebus, Susanne, additional, Knapp, Michael, additional, Neuhaus, Horst, additional, Rösch, Thomas, additional, Ell, Christian, additional, Gockel, Ines, additional, Schumacher, Johannes, additional, and Böhmer, Anne C., additional

Published
2019
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138. No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study

Author

Dong, Jing, primary, Gharahkhani, Puya, additional, Chow, Wong-Ho, additional, Gammon, Marilie D., additional, Liu, Geoffrey, additional, Caldas, Carlos, additional, Wu, Anna H., additional, Ye, Weimin, additional, Onstad, Lynn, additional, Anderson, Lesley A., additional, Bernstein, Leslie, additional, Pharoah, Paul D., additional, Risch, Harvey A., additional, Corley, Douglas A., additional, Fitzgerald, Rebecca C., additional, Iyer, Prasad G., additional, Reid, Brian J., additional, Lagergren, Jesper, additional, Shaheen, Nicholas J., additional, Vaughan, Thomas L., additional, MacGregor, Stuart, additional, Love, Sharon, additional, Palles, Claire, additional, Tomlinson, Ian, additional, Gockel, Ines, additional, May, Andrea, additional, Gerges, Christian, additional, Anders, Mario, additional, Böhmer, Anne C., additional, Becker, Jessica, additional, Kreuser, Nicole, additional, Thieme, Rene, additional, Noder, Tania, additional, Venerito, Marino, additional, Veits, Lothar, additional, Schmidt, Thomas, additional, Schmidt, Claudia, additional, Izbicki, Jakob R., additional, Hölscher, Arnulf H., additional, Lang, Hauke, additional, Lorenz, Dietmar, additional, Schumacher, Brigitte, additional, Mayershofer, Rupert, additional, Vashist, Yogesh, additional, Ott, Katja, additional, Vieth, Michael, additional, Weismüller, Josef, additional, Nöthen, Markus M., additional, Moebus, Susanne, additional, Knapp, Michael, additional, Peters, Wilbert H.M., additional, Neuhaus, Horst, additional, Rösch, Thomas, additional, Ell, Christian, additional, Jankowski, Janusz, additional, Schumacher, Johannes, additional, Neale, Rachel E., additional, Whiteman, David C., additional, and Thrift, Aaron P., additional

Published
2019
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142. Distribution of lymph node metastases in esophageal carcinoma [TIGER study] : Study protocol of a multinational observational study

Author

Hagens, Eliza R.C., Van Berge Henegouwen, Mark I., Van Sandick, Johanna W., Cuesta, Miguel A., Van Der Peet, Donald L., Heisterkamp, Joos, Nieuwenhuijzen, Grard A.P., Rosman, Camiel, Scheepers, Joris J.G., Sosef, Meindert N., Van Hillegersberg, Richard, Lagarde, Sjoerd M., Nilsson, Magnus, Räsänen, Jari, Nafteux, Philippe, Pattyn, Piet, Hölscher, Arnulf H., Schröder, Wolfgang, Schneider, Paul M., Mariette, Christophe, Castoro, Carlo, Bonavina, Luigi, Rosati, Riccardo, De Manzoni, Giovanni, Mattioli, Sandro, Garcia, Josep Roig, Pera, Manuel, Griffin, Michael, Wilkerson, Paul, Chaudry, M. Asif, Sgromo, Bruno, Tucker, Olga, Cheong, Edward, Moorthy, Krishna, Walsh, Thomas N., Reynolds, John, Tachimori, Yuji, Inoue, Haruhiro, Matsubara, Hisahiro, Kosugi, Shin Ichi, Chen, Haiquan, Law, Simon Y.K., Pramesh, C. S., Puntambekar, Shailesh P., Murthy, Sudish, Linden, Philip, Hofstetter, Wayne L., Kuppusamy, Madhan K., Shen, K. Robert, Darling, Gail E., Sabino, Flávio D., Grimminger, Peter P., Meijer, Sybren L., Bergman, Jacques J.G.H.M., Hulshof, Maarten C.C.M., Van Laarhoven, Hanneke W.M., Mearadji, Banafsche, Bennink, Roel J., Annema, Jouke T., Dijkgraaf, Marcel G.W., Gisbertz, Suzanne S., Hagens, Eliza R.C., Van Berge Henegouwen, Mark I., Van Sandick, Johanna W., Cuesta, Miguel A., Van Der Peet, Donald L., Heisterkamp, Joos, Nieuwenhuijzen, Grard A.P., Rosman, Camiel, Scheepers, Joris J.G., Sosef, Meindert N., Van Hillegersberg, Richard, Lagarde, Sjoerd M., Nilsson, Magnus, Räsänen, Jari, Nafteux, Philippe, Pattyn, Piet, Hölscher, Arnulf H., Schröder, Wolfgang, Schneider, Paul M., Mariette, Christophe, Castoro, Carlo, Bonavina, Luigi, Rosati, Riccardo, De Manzoni, Giovanni, Mattioli, Sandro, Garcia, Josep Roig, Pera, Manuel, Griffin, Michael, Wilkerson, Paul, Chaudry, M. Asif, Sgromo, Bruno, Tucker, Olga, Cheong, Edward, Moorthy, Krishna, Walsh, Thomas N., Reynolds, John, Tachimori, Yuji, Inoue, Haruhiro, Matsubara, Hisahiro, Kosugi, Shin Ichi, Chen, Haiquan, Law, Simon Y.K., Pramesh, C. S., Puntambekar, Shailesh P., Murthy, Sudish, Linden, Philip, Hofstetter, Wayne L., Kuppusamy, Madhan K., Shen, K. Robert, Darling, Gail E., Sabino, Flávio D., Grimminger, Peter P., Meijer, Sybren L., Bergman, Jacques J.G.H.M., Hulshof, Maarten C.C.M., Van Laarhoven, Hanneke W.M., Mearadji, Banafsche, Bennink, Roel J., Annema, Jouke T., Dijkgraaf, Marcel G.W., and Gisbertz, Suzanne S.

Published
2019

143. Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: Study protocol of a multinational observational study

Author

Divisie Beeld & Oncologie, Cancer, Hagens, Eliza R.C., Van Berge Henegouwen, Mark I., Van Sandick, Johanna W., Cuesta, Miguel A., Van Der Peet, Donald L., Heisterkamp, Joos, Nieuwenhuijzen, Grard A.P., Rosman, Camiel, Scheepers, Joris J.G., Sosef, Meindert N., Van Hillegersberg, Richard, Lagarde, Sjoerd M., Nilsson, Magnus, Räsänen, Jari, Nafteux, Philippe, Pattyn, Piet, Hölscher, Arnulf H., Schröder, Wolfgang, Schneider, Paul M., Mariette, Christophe, Castoro, Carlo, Bonavina, Luigi, Rosati, Riccardo, De Manzoni, Giovanni, Mattioli, Sandro, Garcia, Josep Roig, Pera, Manuel, Griffin, Michael, Wilkerson, Paul, Chaudry, M. Asif, Sgromo, Bruno, Tucker, Olga, Cheong, Edward, Moorthy, Krishna, Walsh, Thomas N., Reynolds, John, Tachimori, Yuji, Inoue, Haruhiro, Matsubara, Hisahiro, Kosugi, Shin Ichi, Chen, Haiquan, Law, Simon Y.K., Pramesh, C. S., Puntambekar, Shailesh P., Murthy, Sudish, Linden, Philip, Hofstetter, Wayne L., Kuppusamy, Madhan K., Shen, K. Robert, Darling, Gail E., Sabino, Flávio D., Grimminger, Peter P., Meijer, Sybren L., Bergman, Jacques J.G.H.M., Hulshof, Maarten C.C.M., Van Laarhoven, Hanneke W.M., Mearadji, Banafsche, Bennink, Roel J., Annema, Jouke T., Dijkgraaf, Marcel G.W., Gisbertz, Suzanne S., Divisie Beeld & Oncologie, Cancer, Hagens, Eliza R.C., Van Berge Henegouwen, Mark I., Van Sandick, Johanna W., Cuesta, Miguel A., Van Der Peet, Donald L., Heisterkamp, Joos, Nieuwenhuijzen, Grard A.P., Rosman, Camiel, Scheepers, Joris J.G., Sosef, Meindert N., Van Hillegersberg, Richard, Lagarde, Sjoerd M., Nilsson, Magnus, Räsänen, Jari, Nafteux, Philippe, Pattyn, Piet, Hölscher, Arnulf H., Schröder, Wolfgang, Schneider, Paul M., Mariette, Christophe, Castoro, Carlo, Bonavina, Luigi, Rosati, Riccardo, De Manzoni, Giovanni, Mattioli, Sandro, Garcia, Josep Roig, Pera, Manuel, Griffin, Michael, Wilkerson, Paul, Chaudry, M. Asif, Sgromo, Bruno, Tucker, Olga, Cheong, Edward, Moorthy, Krishna, Walsh, Thomas N., Reynolds, John, Tachimori, Yuji, Inoue, Haruhiro, Matsubara, Hisahiro, Kosugi, Shin Ichi, Chen, Haiquan, Law, Simon Y.K., Pramesh, C. S., Puntambekar, Shailesh P., Murthy, Sudish, Linden, Philip, Hofstetter, Wayne L., Kuppusamy, Madhan K., Shen, K. Robert, Darling, Gail E., Sabino, Flávio D., Grimminger, Peter P., Meijer, Sybren L., Bergman, Jacques J.G.H.M., Hulshof, Maarten C.C.M., Van Laarhoven, Hanneke W.M., Mearadji, Banafsche, Bennink, Roel J., Annema, Jouke T., Dijkgraaf, Marcel G.W., and Gisbertz, Suzanne S.

Published
2019

144. The economic burden of endoscopic treatment for anastomotic leaks following oncological Ivor Lewis esophagectomy

Author

Kamolz, Lars-Peter, Baltin, Christoph, Kron, Florian, Urbanski, Alexander, Zander, Thomas, Kron, Anna, Berlth, Felix, Kleinert, Robert, Hallek, Michael, Hölscher, Arnulf H., Chon, Seung-Hun, Kamolz, Lars-Peter, Baltin, Christoph, Kron, Florian, Urbanski, Alexander, Zander, Thomas, Kron, Anna, Berlth, Felix, Kleinert, Robert, Hallek, Michael, Hölscher, Arnulf H., and Chon, Seung-Hun

Abstract

Background: Complications after surgery for esophageal cancer are associated with significant resource utilization. The aim of this study was to analyze the economic burden of two frequently used endoscopic treatments for anastomotic leak management after esophageal surgery: Treatment with a Self-expanding Metal Stent (SEMS) and Endoscopic Vacuum Therapy (EVT). Materials and methods: Between January 2012 and December 2016, we identified 60 German-Diagnosis Related Group (G-DRG) cases of patients who received a SEMS and / or EVT for esophageal anastomotic leaks. Direct costs per case were analyzed according to the Institute for Remuneration System in Hospitals (InEK) cost-accounting approach by comparing DRG payments on the case level, including all extra fees per DRG catalogue. Results: In total, 60 DRG cases were identified. Of these, 15 patients were excluded because they received a combination of SEMS and EVT. Another 6 cases could not be included due to incomplete DRG data. Finally, N = 39 DRG cases were analyzed from a profit-center perspective. A further analysis of the most frequent DRG code -G03- including InEK cost accounting, revealed almost twice the deficit for the EVT group (N = 13 cases, € - 9.282 per average case) compared to that for the SEMS group (N = 9 cases, € - 5.156 per average case). Conclusion: Endoscopic treatments with SEMS and EVT for anastomotic leaks following oncological Ivor Lewis esophagectomies are not cost-efficient for German hospitals. Due to longer hospitalization and insufficient reimbursements, EVT is twice as costly as SEMS treatment. An adequate DRG cost compensation is needed for SEMS and EVT.

Published
2019

145. The expression of the immune checkpoint regulator VISTA correlates with improved overall survival in pT1/2 tumor stages in esophageal adenocarcinoma

Author

Löser, Heike, Krämer, Max, Gebauer, Florian, Bruns, Christiane, Schröder, Wolfgang, Zander, Thomas, Persa, Oana-Diana, Alakus, Hakan, Hölscher, Arnulf H., Büttner, Reinhard, Lohneis, Philipp, Quaas, Alexander, Löser, Heike, Krämer, Max, Gebauer, Florian, Bruns, Christiane, Schröder, Wolfgang, Zander, Thomas, Persa, Oana-Diana, Alakus, Hakan, Hölscher, Arnulf H., Büttner, Reinhard, Lohneis, Philipp, and Quaas, Alexander

Abstract

Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for long-term survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.

Published
2019

146. HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma

Author

Plum, Patrick Sven, Gebauer, Florian, Krämer, Max, Alakus, Hakan, Berlth, Felix, Chon, Seung-Hun, Schiffmann, Lars, Zander, Thomas, Büttner, Reinhard, Hölscher, Arnulf H., Bruns, Christiane, Quaas, Alexander, Löser, Heike, Plum, Patrick Sven, Gebauer, Florian, Krämer, Max, Alakus, Hakan, Berlth, Felix, Chon, Seung-Hun, Schiffmann, Lars, Zander, Thomas, Büttner, Reinhard, Hölscher, Arnulf H., Bruns, Christiane, Quaas, Alexander, and Löser, Heike

Abstract

Background: HER2 (ERBB2 or HER2/neu) is a tyrosine-kinase increasing cell proliferation. Overexpression/amplification of HER2 is correlated with worse prognosis in solid malignancies. Consequently, HER2 targeting is established in breast and upper gastrointestinal tract cancer. There are conflicting data concerning the impact of HER2 overexpression on esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus/gastroesophageal junction and the stomach. The aim of this study was to analyze the expression/amplification of HER2 in EAC in correlation to clinicopathological data to verify its prognostic impact. Methods: We analyzed 428 EAC patients that underwent transthoracic thoraco-abdominal esophagectomy between 1997 and 2014. We performed HER2 immunohistochemistry (IHC) according to the guidelines and fluorescence-in-situ-hybridization (FISH) for IHC score2+, using tissue micro arrays (TMA) with up to eight biopsies from the surface and infiltration area of a single tumor for evaluating HER2-heterogeneity and single-spot TMA. The HER2-status was correlated with clinicopathological data. Results: HER2-positivity was found in up to 14.9% in our cohort (IHC score 3+ or IHC score 2+ with gene amplification) and demonstrated a significantly better overall survival (OS) in correlation to HER2-negative tumors (median OS 70.1 vs. 24.6 months, p = 0.006). HER2-overexpression was more frequently seen in lower tumor stages (pT1/pT2, p = 0.038), in the absence of lymphatic metastases (pN0/pN+, p = 0.020), and was significantly associated with better histological grading (G1/G2) (p = 0.041). Conclusion: We demonstrated a positive prognostic impact of HER2 overexpression in a large cohort of EAC, contrary to other solid malignancies including gastric cancer and breast cancer, but consistent to the results of a large study on EAC from 2012.

Published
2019

149. Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study

Author

Hewitt, Lindsay C., Inam, Imran Z., Saito, Yuichi, Yoshikawa, Takaki, Quaas, Alexander, Hölscher, Arnulf H., Bollschweiler, Elfriede, Fazzi, Gregorio E., Melotte, Veerle, Langley, Ruth Elizabeth, Nankivell, Matthew, Cunningham, David, Allum, William, Hutchins, Gordon G., Grabsch, Heike Irmgard, Clinical Genetics, Promovendi ODB, Pathologie, and RS: GROW - R2 - Basic and Translational Cancer Biology

Subjects
HIGH-INCIDENCE AREA, Epsteine-Barr virus, Oesophageal cancer, DNA mismatch repair, COLON-CANCER, NONPOLYPOSIS COLORECTAL-CANCER, RANDOMIZED PHASE-3 TRIAL, OPEN-LABEL, PD-1 BLOCKADE, DOUBLE-BLIND, MICROSATELLITE-INSTABILITY, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, Microsatellite instability, ddc:610, SQUAMOUS-CELL CARCINOMA, CLINICAL-PRACTICE GUIDELINES, Gastric cancer
Abstract

Background: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/ or EpsteineBarr virus (EBV) status. The aim of this study was to establish and compare EBV status and MMR status in large multi-centre series of OeC and GC. Methods: EBV was assessed by EBV-encoded RNA (EBER) in situ hybridisation and MMR protein expression by immunohistochemistry (IHC) in 988 OeC and 1213 GC from multiple centres. In a subset of OeC, microsatellite instability (MSI) was tested in parallel with MMR IHC. Results: Frequency of MMR deficiency (MMRdef) and MSI was low in OeC (0.8% and 0.6%, respectively) compared with GC (10.3%). None of the OeCs were EBER positive in contrast to 4.8% EBER positive GC. EBV positive GC patients were younger (p = 0.01), more often male (p = 0.001) and had a better overall survival (p = 0.012). MMRdef GC patients were older (p = 0.001) and showed more often intestinal-type histology (p = 0.022). Conclusions: This is the largest study to date indicating that EBV and MMRdef do not play a role in OeC carcinogenesis in contrast to GC. The potential clinical usefulness of determining MMRdef/EBV status to screen patients for eligibility for immune-targeting therapy differs between OeC and GC patients. (C) 2018 The Authors. Published by Elsevier Ltd.

Published
2018

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