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2. Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe

Author

Kroese, T.E. van Laarhoven, H.W.M. Schoppman, S.F. Deseyne, P.R.A.J. van Cutsem, E. Haustermans, K. Nafteux, P. Thomas, M. Obermannova, R. Mortensen, H.R. Nordsmark, M. Pfeiffer, P. Elme, A. Adenis, A. Piessen, G. Bruns, C.J. Lordick, F. Gockel, I. Moehler, M. Gani, C. Liakakos, T. Reynolds, J. Morganti, A.G. Rosati, R. Castoro, C. Cellini, F. D'Ugo, D. Roviello, F. Bencivenga, M. de Manzoni, G. van Berge Henegouwen, M.I. Hulshof, M.C.C.M. van Dieren, J. Vollebergh, M. van Sandick, J.W. Jeene, P. Muijs, C.T. Slingerland, M. Voncken, F.E.M. Hartgrink, H. Creemers, G.-J. van der Sangen, M.J.C. Nieuwenhuijzen, G. Berbee, M. Verheij, M. Wijnhoven, B. Beerepoot, L.V. Mohammad, N.H. Mook, S. Ruurda, J.P. Kolodziejczyk, P. Polkowski, W.P. Wyrwicz, L. Alsina, M. Pera, M. Kanonnikoff, T.F. Cervantes, A. Nilsson, M. Monig, S. Wagner, A.D. Guckenberger, M. Griffiths, E.A. Smyth, E. Hanna, G.B. Markar, S. Chaudry, M.A. Hawkins, M.A. Cheong, E. van Hillegersberg, R. van Rossum, P.S.N. Rozema, T. Heisterkamp, J. Schaefer, M. Ozsahin, E.-M. de Haan, J. Willem van den Berg, J. Duprez, F. Callebout, E. van Daele, E. Hacker, U. Hoffmeister, A. Kuhnt, T. Denecke, T. Kluge, R. Prager, G. Ilhan-Mutlu, A. Cuicchi, D. Ardizzoni, A. Rosman, C. Gootjes, E.C. Rütten, H. Puccetti, F. Cascinu, S. Slim, N. Barrios, M.E. Fernandez, M.C. Martí-Oriol, R. Alvaro, M.H. Vera, A. Jordá, E. Mozos, F.L. Reig, A. Visa, L. Ciseł, B. Czechowska, J. Kwietniewska, M. Pikuła, A. Skórzewska, M. Kozłowska, A. Rawicz-Pruszyński, K. the OMEC collaborators and Kroese, T.E. van Laarhoven, H.W.M. Schoppman, S.F. Deseyne, P.R.A.J. van Cutsem, E. Haustermans, K. Nafteux, P. Thomas, M. Obermannova, R. Mortensen, H.R. Nordsmark, M. Pfeiffer, P. Elme, A. Adenis, A. Piessen, G. Bruns, C.J. Lordick, F. Gockel, I. Moehler, M. Gani, C. Liakakos, T. Reynolds, J. Morganti, A.G. Rosati, R. Castoro, C. Cellini, F. D'Ugo, D. Roviello, F. Bencivenga, M. de Manzoni, G. van Berge Henegouwen, M.I. Hulshof, M.C.C.M. van Dieren, J. Vollebergh, M. van Sandick, J.W. Jeene, P. Muijs, C.T. Slingerland, M. Voncken, F.E.M. Hartgrink, H. Creemers, G.-J. van der Sangen, M.J.C. Nieuwenhuijzen, G. Berbee, M. Verheij, M. Wijnhoven, B. Beerepoot, L.V. Mohammad, N.H. Mook, S. Ruurda, J.P. Kolodziejczyk, P. Polkowski, W.P. Wyrwicz, L. Alsina, M. Pera, M. Kanonnikoff, T.F. Cervantes, A. Nilsson, M. Monig, S. Wagner, A.D. Guckenberger, M. Griffiths, E.A. Smyth, E. Hanna, G.B. Markar, S. Chaudry, M.A. Hawkins, M.A. Cheong, E. van Hillegersberg, R. van Rossum, P.S.N. Rozema, T. Heisterkamp, J. Schaefer, M. Ozsahin, E.-M. de Haan, J. Willem van den Berg, J. Duprez, F. Callebout, E. van Daele, E. Hacker, U. Hoffmeister, A. Kuhnt, T. Denecke, T. Kluge, R. Prager, G. Ilhan-Mutlu, A. Cuicchi, D. Ardizzoni, A. Rosman, C. Gootjes, E.C. Rütten, H. Puccetti, F. Cascinu, S. Slim, N. Barrios, M.E. Fernandez, M.C. Martí-Oriol, R. Alvaro, M.H. Vera, A. Jordá, E. Mozos, F.L. Reig, A. Visa, L. Ciseł, B. Czechowska, J. Kwietniewska, M. Pikuła, A. Skórzewska, M. Kozłowska, A. Rawicz-Pruszyński, K. the OMEC collaborators

Abstract

Background: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. Methods: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%–75%) or consensus (≥75%). Results: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). Conclusion: The OMEC project has

Published
2023

3. Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe

Author

Kroese, T.E., Laarhoven, H.W.M. van, Schoppman, S.F., Deseyne, P., Cutsem, E. Van, Haustermans, K., Nafteux, P., Thomas, M., Obermannova, R., Mortensen, H.R., Nordsmark, M., Pfeiffer, P., Elme, A., Adenis, A., Piessen, G., Bruns, C.J., Lordick, F., Gockel, I., Moehler, M., Gani, C., Liakakos, T., Reynolds, J., Morganti, A.G., Rosati, R., Castoro, C., Cellini, F., D'Ugo, D., Roviello, F., Bencivenga, M., Manzoni, G. de, Henegouwen, M.I. van Berge, Hulshof, M., Dieren, J. van, Vollebergh, M., Sandick, J.W. van, Jeene, P., Muijs, C.T., Slingerland, M., Voncken, F.E.M., Hartgrink, H., Creemers, G.J., Sangen, M.J. van der, Nieuwenhuijzen, G., Berbee, M., Verheij, M., Wijnhoven, B., Beerepoot, L.V., Mohammad, N.H., Mook, S., Ruurda, J.P., Kolodziejczyk, P., Polkowski, W.P., Wyrwicz, L., Alsina, M., Pera, M., Kanonnikoff, T.F., Cervantes, A., Nilsson, M., Monig, S., Wagner, A.D., Guckenberger, M., Griffiths, E.A., Smyth, E., Hanna, G.B., Markar, S., Chaudry, M.A., Hawkins, M.A., Cheong, E., Rütten, H., Gootjes, E.C., Hillegersberg, R. van, Rossum, P.S.N. van, Kroese, T.E., Laarhoven, H.W.M. van, Schoppman, S.F., Deseyne, P., Cutsem, E. Van, Haustermans, K., Nafteux, P., Thomas, M., Obermannova, R., Mortensen, H.R., Nordsmark, M., Pfeiffer, P., Elme, A., Adenis, A., Piessen, G., Bruns, C.J., Lordick, F., Gockel, I., Moehler, M., Gani, C., Liakakos, T., Reynolds, J., Morganti, A.G., Rosati, R., Castoro, C., Cellini, F., D'Ugo, D., Roviello, F., Bencivenga, M., Manzoni, G. de, Henegouwen, M.I. van Berge, Hulshof, M., Dieren, J. van, Vollebergh, M., Sandick, J.W. van, Jeene, P., Muijs, C.T., Slingerland, M., Voncken, F.E.M., Hartgrink, H., Creemers, G.J., Sangen, M.J. van der, Nieuwenhuijzen, G., Berbee, M., Verheij, M., Wijnhoven, B., Beerepoot, L.V., Mohammad, N.H., Mook, S., Ruurda, J.P., Kolodziejczyk, P., Polkowski, W.P., Wyrwicz, L., Alsina, M., Pera, M., Kanonnikoff, T.F., Cervantes, A., Nilsson, M., Monig, S., Wagner, A.D., Guckenberger, M., Griffiths, E.A., Smyth, E., Hanna, G.B., Markar, S., Chaudry, M.A., Hawkins, M.A., Cheong, E., Rütten, H., Gootjes, E.C., Hillegersberg, R. van, and Rossum, P.S.N. van

Abstract

Item does not contain fulltext, BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resul

Published
2023

4. Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe

Author

Kroese, T.E. van Hillegersberg, R. Schoppmann, S. Deseyne, P.R.A.J. Nafteux, P. Obermannova, R. Nordsmark, M. Pfeiffer, P. Hawkings, M.A. Smyth, E. Markar, S. Hanna, G.B. Cheong, E. Chaudry, A. Elme, A. Adenis, A. Piessen, G. Gani, C. Bruns, C.J. Moehler, M. Liakakos, T. Reynolds, J. Morganti, A. Rosati, R. Castoro, C. D'Ugo, D. Roviello, F. Bencivenga, M. de Manzoni, G. Jeene, P. van Sandick, J.W. Muijs, C. Slingerland, M. Nieuwenhuijzen, G. Wijnhoven, B. Beerepoot, L.V. Kolodziejczyk, P. Polkowski, W.P. Alsina, M. Pera, M. Kanonnikoff, T.F. Nilsson, M. Guckenberger, M. Monig, S. Wagner, D. Wyrwicz, L. Berbee, M. Gockel, I. Lordick, F. Griffiths, E.A. Verheij, M. van Rossum, P.S.N. van Laarhoven, H.W.M. Rosman, C. Rütten, H. Gootjes, E.C. Vonken, F.E.M. van Dieren, J.M. Vollebergh, M.A. van der Sangen, M. Creemers, G.-J. Zander, T. Schlößer, H. Cascinu, S. Mazza, E. Nicoletti, R. Damascelli, A. Slim, N. Passoni, P. Cossu, A. Puccetti, F. Barbieri, L. Fanti, L. Azzolini, F. Ventoruzzo, F. Szczepanik, A. Visa, L. Reig, A. Roques, T. Harrison, M. Ciseł, B. Pikuła, A. Skórzewska, M. Vanommeslaeghe, H. Van Daele, E. Pattyn, P. Geboes, K. Callebout, E. Ribeiro, S. van Duijvendijk, P. Tromp, C. Sosef, M. Warmerdam, F. Heisterkamp, J. Vera, A. Jordá, E. López-Mozos, F. Fernandez-Moreno, M.C. Barrios-Carvajal, M. Huerta, M. de Steur, W. Lips, I. Diez, M. Castro, S. O'Neill, R. Holyoake, D. Hacker, U. Denecke, T. Kuhnt, T. Hoffmeister, A. Kluge, R. Bostel, T. Grimminger, P. Jedlička, V. Křístek, J. Pospíšil, P. Mourregot, A. Maurin, C. Starling, N. Chong, I. OMEC working group and Kroese, T.E. van Hillegersberg, R. Schoppmann, S. Deseyne, P.R.A.J. Nafteux, P. Obermannova, R. Nordsmark, M. Pfeiffer, P. Hawkings, M.A. Smyth, E. Markar, S. Hanna, G.B. Cheong, E. Chaudry, A. Elme, A. Adenis, A. Piessen, G. Gani, C. Bruns, C.J. Moehler, M. Liakakos, T. Reynolds, J. Morganti, A. Rosati, R. Castoro, C. D'Ugo, D. Roviello, F. Bencivenga, M. de Manzoni, G. Jeene, P. van Sandick, J.W. Muijs, C. Slingerland, M. Nieuwenhuijzen, G. Wijnhoven, B. Beerepoot, L.V. Kolodziejczyk, P. Polkowski, W.P. Alsina, M. Pera, M. Kanonnikoff, T.F. Nilsson, M. Guckenberger, M. Monig, S. Wagner, D. Wyrwicz, L. Berbee, M. Gockel, I. Lordick, F. Griffiths, E.A. Verheij, M. van Rossum, P.S.N. van Laarhoven, H.W.M. Rosman, C. Rütten, H. Gootjes, E.C. Vonken, F.E.M. van Dieren, J.M. Vollebergh, M.A. van der Sangen, M. Creemers, G.-J. Zander, T. Schlößer, H. Cascinu, S. Mazza, E. Nicoletti, R. Damascelli, A. Slim, N. Passoni, P. Cossu, A. Puccetti, F. Barbieri, L. Fanti, L. Azzolini, F. Ventoruzzo, F. Szczepanik, A. Visa, L. Reig, A. Roques, T. Harrison, M. Ciseł, B. Pikuła, A. Skórzewska, M. Vanommeslaeghe, H. Van Daele, E. Pattyn, P. Geboes, K. Callebout, E. Ribeiro, S. van Duijvendijk, P. Tromp, C. Sosef, M. Warmerdam, F. Heisterkamp, J. Vera, A. Jordá, E. López-Mozos, F. Fernandez-Moreno, M.C. Barrios-Carvajal, M. Huerta, M. de Steur, W. Lips, I. Diez, M. Castro, S. O'Neill, R. Holyoake, D. Hacker, U. Denecke, T. Kuhnt, T. Hoffmeister, A. Kluge, R. Bostel, T. Grimminger, P. Jedlička, V. Křístek, J. Pospíšil, P. Mourregot, A. Maurin, C. Starling, N. Chong, I. OMEC working group

Abstract

Background: Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. Objective: To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. Material and methods: European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%–75%), or consensus (≥75%). Results: A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1–2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease. Conclusion: A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of o

Published
2022

5. Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe

Author

Kroese, T.E., Hillegersberg, R. van, Schoppmann, S., Deseyne, P., Nafteux, P., Obermannova, R., Nordsmark, M., Pfeiffer, P., Hawkins, M.A., Smyth, E., Markar, S., Hanna, G.B., Cheong, E., Chaudry, A., Elme, A., Adenis, A., Piessen, G., Gani, C., Bruns, C.J., Moehler, M., Liakakos, T., Reynolds, J., Morganti, A., Rosati, R., Castoro, C., D'Ugo, D., Roviello, F., Bencivenga, M., Manzoni, G. de, Jeene, P., Sandick, J.W. van, Muijs, C., Slingerland, M., Nieuwenhuijzen, G., Wijnhoven, B., Beerepoot, L.V., Kolodziejczyk, P., Polkowski, W.P., Alsina, M., Pera, M., Kanonnikoff, T.F., Nilsson, M., Guckenberger, M., Monig, S., Wagner, D., Wyrwicz, L., Berbee, M., Gockel, I., Lordick, F., Griffiths, E.A., Rütten, H., Rosman, C., Verheij, M., Rossum, P.S.N. van, Laarhoven, H.W. van, Kroese, T.E., Hillegersberg, R. van, Schoppmann, S., Deseyne, P., Nafteux, P., Obermannova, R., Nordsmark, M., Pfeiffer, P., Hawkins, M.A., Smyth, E., Markar, S., Hanna, G.B., Cheong, E., Chaudry, A., Elme, A., Adenis, A., Piessen, G., Gani, C., Bruns, C.J., Moehler, M., Liakakos, T., Reynolds, J., Morganti, A., Rosati, R., Castoro, C., D'Ugo, D., Roviello, F., Bencivenga, M., Manzoni, G. de, Jeene, P., Sandick, J.W. van, Muijs, C., Slingerland, M., Nieuwenhuijzen, G., Wijnhoven, B., Beerepoot, L.V., Kolodziejczyk, P., Polkowski, W.P., Alsina, M., Pera, M., Kanonnikoff, T.F., Nilsson, M., Guckenberger, M., Monig, S., Wagner, D., Wyrwicz, L., Berbee, M., Gockel, I., Lordick, F., Griffiths, E.A., Rütten, H., Rosman, C., Verheij, M., Rossum, P.S.N. van, and Laarhoven, H.W. van

Abstract

Item does not contain fulltext, BACKGROUND: Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking. OBJECTIVE: To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe. MATERIAL AND METHODS: European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%-75%), or consensus (≥75%). RESULTS: A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1-2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease. CONCLUSION: A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oeso

Published
2022

7. 706. Haematological toxicity associated with hyperthermic intraperitoneal chemotherapy: Comparison of mitomycin C and oxaliplatin

Author

Lewicka, M., primary, Ciseł, B., additional, Skórzewska, M., additional, Pikuła, A., additional, Cisło, M., additional, Mielko, J., additional, Sitarz, R., additional, Jazienicki, M., additional, Sokoluk, M., additional, Zuchora, B., additional, Kurylcio, A., additional, Rawicz-Pruszyński, K., additional, and Polkowski, W.P., additional

Published
2016
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18. Molecular and pro-inflammatory genetic profile in gastric carcinomas

Author

Infection & Immunity, Pathologie, Offerhaus, G.J.A., Maciejewski, R., Polkowski, W.P., Milne - Blaney, A.N.A., de Leng, WW, Sitarz, R., Infection & Immunity, Pathologie, Offerhaus, G.J.A., Maciejewski, R., Polkowski, W.P., Milne - Blaney, A.N.A., de Leng, WW, and Sitarz, R.

Published
2009

26. Perspective on breast and axilla preservation after introduction of targeted intraoperative radiotherapy and sentinel node biopsy for the treatment of patients with early breast carcinoma

Author

Polkowski, W.P., primary, Romanek, J., additional, Kurylcio, A., additional, Jankiewicz, M., additional, Winkler, B., additional, Lewicka, M., additional, Mielko, J., additional, Golebiewska, R., additional, Chrapko, B., additional, and Stanislawek, A., additional

Published
2008
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27. Cyclooxygenase-2 mediated regulation of E-cadherin occurs in conventional but not early-onset gastric cancer cell lines

Author

Leguit, R.J., de Leng, W.W.J., Morsink, F.H.M., Polkowski, W.P., Maciejewski, R., and Milne, A.N.

Abstract

Background: COX-2 and E-cadherin, involved in invasion and metastasis, are molecules critical for gastric carcinogenesis. A relationship between them is documented in non-small cell lung and prostate cancer. We present novel evidence of a relationship between COX-2 and E-cadherin expression in gastric cancer.Methods: Using qPCR and Western blots analysis on celecoxib and PGE2 treated and untreated gastric cancer cell lines derived from tumours of the intestinal type (MKN45, MKN28, AGS3, MKN7) and immunohistochemistry of 178 gastric cancers on tissue microarrays (TMA), we examined the COX-2/E-cadherin relationship.Results: Down-regulation of COX-2 by celecoxib led to up-regulation of E-cadherin mRNA and protein levels in conventional gastric cancer cell lines, whereas expression was down regulated in the early-onset gastric cancer (EOGC) cell line. Immunohistochemistry on TMAs of 178 gastric cancers showed no correlation between COX-2 and E-cadherin expression in the conventional or early gastric cancer groups.Conclusion: The results suggest that COX-2 has an impact on transcriptional regulation of E-cadherin in gastric cancer and our findings further highlight the intriguing nature of EOGCs which appear to have a molecular phenotype distinct from conventional gastric cancer. In addition, our findings also suggest that reduction of COX-2 using nonsteroidal anti-inflammatory drugs in gastric cancer chemoprevention may only be relevant for older patients.

Published
2009
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29. Molecular and pro-inflammatory genetic profile in gastric carcinomas

Author

Sitarz, R., Offerhaus, G.J.A., Maciejewski, R., Polkowski, W.P., Milne - Blaney, A.N.A., de Leng, WW, and University Utrecht

Subjects
digestive, oral, and skin physiology, digestive system diseases
Abstract

Gastric cancer is a result from the combination of environmental factors and an accumulation of specific genetic alterations, and affects mainly the older population. It is known that genetic factors play a more important role in early onset gastric cancers than in conventional gastric cancer patients as they have experienced less exposure to environmental factors. It is postulated that EOGC is a key tool in the explanation of the role of genetic changes in gastric carcinogenesis. The specific pathogenetic changes underlying gastric carcinogenesis remain largely unknown. The aim of this thesis is to uncover genetic alterations relevant to gastric carcinogenesis and to elucidate the role of the genes and proteins involved in the progress of cancer in different sub-types of gastric cancers. Additionally, we try to find the best approach for early diagnostics of gastric stump cancers. Gastric cancer is considered a multistep process and multifactor process. An overview of the involved factors as well as important genes in gastric carcinogenesis is provided in chapters 1 and 2. In these chapters the background of gastric cancer is extensively discussed. Additionally in these chapters the concept of early onset gastric cancer is introduced together with the reasoning behind the study of this subtype of gastric cancer. Chapter 3 focuses on a comparison between molecular alterations occurring in primary gastric cancers, corresponding xenografts and gastric carcinoma cell lines. Chapter 4 takes a step towards a better understanding of the progression of gastric carcinogenesis in early onset and conventional gastric cancers. Using Western blot, Q-PCR and sequencing analysis, we examined the correlation between two critical molecules in the development and progression of gastric cancer: COX-2 and E-cadherin. The relationship between these two molecules was examined in vitro in a panel of cell lines and in vivo using tissue microarrays. In chapter 5 we examine the COX-2 -765 G/C promoter polymorphism in different subtypes of gastric cancer. Real time PCR, sequencing analysis and immunohistochemical staining on tissue microarrays were used to find differences between EOGC, conventional gastric cancer and gastric stump cancer. Chapter 6 takes a look into the IL-1B -31 T/C polymorphism distribution in EOGC, conventional and gastric stump cancers using the same techniques as described in chapter 5. Chapter 7 reviews the literature on gastric stump cancer and its precursor lesions and focuses on the reliability of early diagnosis. Finally, chapters 8 and 9 provide brief summaries and a discussion of the thesis (in English and in Dutch respectively).

Published
2009

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