Search

Your search keyword '"Seppälä, Toni T."' showing total 328 results
Start Over Author "Seppälä, Toni T."
328 results on '"Seppälä, Toni T."'

5. Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement

Author

Møller, Pal, Seppälä, Toni T., Ahadova, Aysel, Crosbie, Emma J., Holinski-Feder, Elke, Scott, Rodney, Haupt, Saskia, Möslein, Gabriela, Winship, Ingrid, Broeke, Sanne W. Bajwa-ten, Kohut, Kelly E., Ryan, Neil, Bauerfeind, Peter, Thomas, Laura E., Evans, D. Gareth, Aretz, Stefan, Sijmons, Rolf H., Half, Elizabeth, Heinimann, Karl, Horisberger, Karoline, Monahan, Kevin, Engel, Christoph, Cavestro, Giulia Martina, Fruscio, Robert, Abu-Freha, Naim, Zohar, Levi, Laghi, Luigi, Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Vaccaro, Carlos, Valle, Adriana Della, Rossi, Benedito Mauro, da Silva, Leandro Apolinário, de Oliveira Nascimento, Ivana Lucia, Rossi, Norma Teresa, Dębniak, Tadeusz, Mecklin, Jukka-Pekka, Bernstein, Inge, Lindblom, Annika, Sunde, Lone, Nakken, Sigve, Heuveline, Vincent, Burn, John, Hovig, Eivind, Kloor, Matthias, Sampson, Julian R., and Dominguez-Valentin, Mev

Published
2023
Full Text
View/download PDF

9. Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement

Author

Maller, Pal, Seppälä, Toni T., Ahadova, Aysel, Crosbie, Emma J., Holinski-Feder, Elke, Scott, Rodney, Haupt, Saskia, Möslein, Gabriela, Winship, Ingrid, Broeke, Sanne W. Bajwa-ten, Kohut, Kelly E., Ryan, Neil, Bauerfeind, Peter, Thomas, Laura E., Evans, D. Gareth, Aretz, Stefan, Sijmons, Rolf H., Half, Elizabeth, Heinimann, Karl, Horisberger, Karoline, Monahan, Kevin, Engel, Christoph, Cavestro, Giulia Martina, Fruscio, Robert, Abu-Freha, Naim, Zohar, Levi, Laghi, Luigi, Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Vaccaro, Carlos, Valle, Adriana Della, Rossi, Benedito Mauro, da Silva, Leandro Apolinário, de Oliveira Nascimento, Ivana Lucia, Rossi, Norma Teresa, DÄbniak, Tadeusz, Mecklin, Jukka-Pekka, Bernstein, Inge, Lindblom, Annika, Sunde, Lone, Nakken, Sigve, Heuveline, Vincent, Burn, John, Hovig, Eivind, Kloor, Matthias, Sampson, Julian R., and Dominguez-Valentin, Mev

Subjects
Aspirin, Stochastic processes, Colorectal cancer -- Genetic aspects -- Development and progression, Immunotherapy, Cancer -- Development and progression -- Genetic aspects, Ovarian cancer -- Development and progression -- Genetic aspects, Health
Abstract

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an 'average sex 'or a pathogenic variant in an 'average Lynch syndrome gene' and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer., Author(s): Pal Maller[sup.1], Toni T. Seppälä[sup.2,3,4], Aysel Ahadova[sup.5,6,7], Emma J. Crosbie[sup.8,9], Elke Holinski-Feder[sup.10,11], Rodney Scott[sup.12], Saskia Haupt[sup.13,14], Gabriela Möslein[sup.15], Ingrid Winship[sup.16,17], Sanne W. Bajwa-ten Broeke[sup.18], Kelly E. Kohut[sup.19], Neil Ryan[sup.20,21], [...]

Published
2023
Full Text
View/download PDF

14. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision

Author

Zaffaroni, Gloria, primary, Mannucci, Alessandro, additional, Koskenvuo, Laura, additional, de Lacy, Borja, additional, Maffioli, Anna, additional, Bisseling, Tanya, additional, Half, Elizabeth, additional, Cavestro, Giulia Martina, additional, Valle, Laura, additional, Ryan, Neil, additional, Aretz, Stefan, additional, Brown, Karen, additional, Buttitta, Francesco, additional, Carneiro, Fatima, additional, Claber, Oonagh, additional, Blanco-Colino, Ruth, additional, Collard, Maxime, additional, Crosbie, Emma, additional, Cunha, Miguel, additional, Doulias, Triantafyllos, additional, Fleming, Christina, additional, Heinrich, Henriette, additional, Hüneburg, Robert, additional, Metras, Julie, additional, Nagtegaal, Iris, additional, Negoi, Ionut, additional, Nielsen, Maartje, additional, Pellino, Gianluca, additional, Ricciardiello, Luigi, additional, Sagir, Abdurrahman, additional, Sánchez-Guillén, Luis, additional, Seppälä, Toni T, additional, Siersema, Peter, additional, Striebeck, Benedikt, additional, Sampson, Julian R, additional, Latchford, Andrew, additional, Parc, Yann, additional, Burn, John, additional, and Möslein, Gabriela, additional

Published
2024
Full Text
View/download PDF

15. Quantitative Multiplexed Analysis of Indoleamine 2,3-Dioxygenase (IDO) and Arginase-1 (ARG1) Expression and Myeloid Cell Infiltration in Colorectal Cancer

Author

Elomaa, Hanna, primary, Härkönen, Jouni, additional, Väyrynen, Sara A., additional, Ahtiainen, Maarit, additional, Ogino, Shuji, additional, Nowak, Jonathan A., additional, Lau, Mai Chan, additional, Helminen, Olli, additional, Wirta, Erkki-Ville, additional, Seppälä, Toni T., additional, Böhm, Jan, additional, Mecklin, Jukka-Pekka, additional, Kuopio, Teijo, additional, and Väyrynen, Juha P., additional

Published
2024
Full Text
View/download PDF

18. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Author

Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Nakken, Sigve, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauß, Hans-Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka-Pekka, Plazzer, John-Paul, Pineda, Marta, Navarro, Matilde, Vidal, Joan Brunet, Kariv, Revital, Rosner, Guy, Piñero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Ryan, Neil, ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, de Vos tot Nederveen Cappel, Wouter H., Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Büttner, Reinhard, Görgens, Heike, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Weitz, Jürgen, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Auranen, Annika, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Denton, Oliver G., Rødland, Einar Andreas, Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Möslein, Gabriela, Sampson, Julian R., Evans, D. Gareth, Seppälä, Toni T., and Møller, Pål

Published
2021
Full Text
View/download PDF

19. High immune cell infiltration predicts improved survival in cholangiocarcinoma.

Author

Wirta, Erkki-Ville, Szeto, Säde, Koppatz, Hanna, Nordin, Arno, Mäkisalo, Heikki, Arola, Johanna, Sirén, Jukka, Ahtiainen, Maarit, Böhm, Jan, Mecklin, Jukka-Pekka, Sallinen, Ville, and Seppälä, Toni T.

Subjects
CHOLANGIOCARCINOMA, PROGRAMMED cell death 1 receptors, PROGRAMMED death-ligand 1, OVERALL survival, PROGNOSIS
Abstract

Background: Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumorinfiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis. Methods: CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells. Results: Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup. Conclusion: Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

21. Multiplexed analysis of macrophage polarisation in pulmonary metastases of microsatellite stable colorectal cancer

Author

Karjula, Topias, primary, Elomaa, Hanna, additional, Väyrynen, Sara A., additional, Kuopio, Teijo, additional, Ahtiainen, Maarit, additional, Mustonen, Olli, additional, Puro, Iiris, additional, Niskakangas, Anne, additional, Mecklin, Jukka-Pekka, additional, Böhm, Jan, additional, Wirta, Erkki-Ville, additional, Seppälä, Toni T., additional, Sihvo, Eero, additional, Yannopoulos, Fredrik, additional, Helminen, Olli, additional, and Väyrynen, Juha, additional

Published
2023
Full Text
View/download PDF

23. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

Author

Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John-Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka-Pekka, Nielsen, Maartje, and Møller, Pål

Published
2020
Full Text
View/download PDF

24. Therapeutic Targeting of Oncogene-induced Transcription-Replication Conflicts in Pancreatic Ductal Adenocarcinoma

Author

Smith, Shanna J, primary, Meng, Fan, additional, Lingeman, Robert, additional, Li, Caroline, additional, Li, Min, additional, Boneh, Galyah, additional, Seppälä, Toni T, additional, Phan, Thuy, additional, Li, Haiqing, additional, Burkhart, Richard A, additional, Parekh, Vishwas, additional, Rahmanuddin, Syed, additional, Melstrom, Laleh G, additional, Hickey, Robert, additional, Chung, Vincent, additional, Liu, Yilun, additional, Malkas, Linda H, additional, and Raoof, Mustafa, additional

Published
2023
Full Text
View/download PDF

27. Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer

Author

Seppälä, Toni T., Zimmerman, Jacquelyn W., Sereni, Elisabetta, Plenker, Dennis, Suri, Reecha, Rozich, Noah, Blair, Alex, Thomas, Dwayne L., II, Teinor, Jonathan, Javed, Ammar, Patel, Hardik, Cameron, John L., Burns, William R., He, Jin, Tuveson, David A., Jaffee, Elizabeth M., Eshleman, James, Szabolcs, Annamaria, Ryan, David P., Ting, David T., Wolfgang, Christopher L., and Burkhart, Richard A.

Published
2020
Full Text
View/download PDF

28. Hereditary colorectal, gastric, and pancreatic cancer : comprehensive review

Author

Seppälä, Toni T., Burkhart, Richard A., Katona, Bryson W., ATG - Applied Tumor Genomics, HUS Abdominal Center, and II kirurgian klinikka

Subjects
Lynch-syndrome, Proximal polyposis, Mismatch repair gene, High-risk individuals, Clinical-practice guidelines, Cost-effectiveness, Germline mutations, 3126 Surgery, anesthesiology, intensive care, radiology, American society, Breast-cancer, Fukuoka guidelines
Abstract

Hereditary gastrointestinal cancers are under-diagnosed and require attention for identification and differential diagnostics with easy access to germline genetic evaluation to confirm the diagnosis. Awareness of multiple predisposing conditions to cancers in various organs, also outside the gastrointestinal tract, is imperative in identification and prompting surveillance and management according to condition-specific clinical guidelines available.Background Inheritance patterns show familial clustering of gastrointestinal cancers, and multiple germline conditions have now been identified that predispose to colorectal, gastric, and pancreatic cancers. Methods A narrative review based on recent relevant literature was conducted. Results Lynch syndrome, formerly known as hereditary non-polyposis colorectal cancer, increases the risk of several abdominal cancers, with the highest population prevalence. Familial adenomatous polyposis and some of the more infrequent polyposis syndromes have distinct characteristics affecting various organ-specific cancer risks. Hereditary gastric and pancreatic cancer syndromes include those also causing colorectal cancer, while additional genetic disorders predisposing only to upper gastrointestinal malignancies have been recognized more recently. Diagnosing and managing hereditary cancer syndromes requires multidisciplinary expertise and may be best managed in tertiary centres, with a need to consider patient preference and ensure shared decision-making. Conclusion Several germline conditions predispose to colorectal, gastric, and pancreatic cancer, which inform identification, surveillance regimens, prevention, cascade screening, counselling, and surgical management. The authors describe developments in the hereditary origin of colorectal, gastric, and pancreatic cancer with current recommendations in surveillance and surgical management.

Published
2023

29. Immunological and prognostic significance of tumour necrosis in colorectal cancer

Author

Kastinen, Meeri, primary, Sirniö, Päivi, additional, Elomaa, Hanna, additional, Ahtiainen, Maarit, additional, Väyrynen, Sara A., additional, Herzig, Karl-Heinz, additional, Meriläinen, Sanna, additional, Aro, Raila, additional, Häivälä, Reetta, additional, Rautio, Tero, additional, Saarnio, Juha, additional, Wirta, Erkki-Ville, additional, Helminen, Olli, additional, Seppälä, Toni T., additional, Kuopio, Teijo, additional, Böhm, Jan, additional, Tuomisto, Anne, additional, Mecklin, Jukka-Pekka, additional, Mäkinen, Markus J., additional, and Väyrynen, Juha P., additional

Published
2023
Full Text
View/download PDF

30. Supplementary Figure from Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up

Author

Mathers, John C., primary, Elliott, Faye, primary, Macrae, Finlay, primary, Mecklin, Jukka-Pekka, primary, Möslein, Gabriela, primary, McRonald, Fiona E., primary, Bertario, Lucio, primary, Evans, D. Gareth, primary, Gerdes, Anne-Marie, primary, Ho, Judy W.C., primary, Lindblom, Annika, primary, Morrison, Patrick J., primary, Rashbass, Jem, primary, Ramesar, Raj S., primary, Seppälä, Toni T., primary, Thomas, Huw J.W., primary, Sheth, Harsh J., primary, Pylvänäinen, Kirsi, primary, Reed, Lynn, primary, Borthwick, Gillian M., primary, Bishop, D. Timothy, primary, and Burn, John, primary

Published
2023
Full Text
View/download PDF

31. Data from Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up

Author

Mathers, John C., primary, Elliott, Faye, primary, Macrae, Finlay, primary, Mecklin, Jukka-Pekka, primary, Möslein, Gabriela, primary, McRonald, Fiona E., primary, Bertario, Lucio, primary, Evans, D. Gareth, primary, Gerdes, Anne-Marie, primary, Ho, Judy W.C., primary, Lindblom, Annika, primary, Morrison, Patrick J., primary, Rashbass, Jem, primary, Ramesar, Raj S., primary, Seppälä, Toni T., primary, Thomas, Huw J.W., primary, Sheth, Harsh J., primary, Pylvänäinen, Kirsi, primary, Reed, Lynn, primary, Borthwick, Gillian M., primary, Bishop, D. Timothy, primary, and Burn, John, primary

Published
2023
Full Text
View/download PDF

32. Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

Author

Dominguez-Valentin, Mev, primary, Haupt, Saskia, additional, Seppälä, Toni T., additional, Sampson, Julian R., additional, Sunde, Lone, additional, Bernstein, Inge, additional, Jenkins, Mark A., additional, Engel, Christoph, additional, Aretz, Stefan, additional, Nielsen, Maartje, additional, Capella, Gabriel, additional, Balaguer, Francesc, additional, Evans, Dafydd Gareth, additional, Burn, John, additional, Holinski-Feder, Elke, additional, Bertario, Lucio, additional, Bonanni, Bernardo, additional, Lindblom, Annika, additional, Levi, Zohar, additional, Macrae, Finlay, additional, Winship, Ingrid, additional, Plazzer, John-Paul, additional, Sijmons, Rolf, additional, Laghi, Luigi, additional, Della Valle, Adriana, additional, Heinimann, Karl, additional, Dębniak, Tadeusz, additional, Fruscio, Robert, additional, Lopez-Koestner, Francisco, additional, Alvarez-Valenzuela, Karin, additional, Katz, Lior H., additional, Laish, Ido, additional, Vainer, Elez, additional, Vaccaro, Carlos, additional, Carraro, Dirce Maria, additional, Monahan, Kevin, additional, Half, Elizabeth, additional, Stakelum, Aine, additional, Winter, Des, additional, Kennelly, Rory, additional, Gluck, Nathan, additional, Sheth, Harsh, additional, Abu-Freha, Naim, additional, Greenblatt, Marc, additional, Rossi, Benedito Mauro, additional, Bohorquez, Mabel, additional, Cavestro, Giulia Martina, additional, Lino-Silva, Leonardo S., additional, Horisberger, Karoline, additional, Tibiletti, Maria Grazia, additional, Nascimento, Ivana do, additional, Thomas, Huw, additional, Rossi, Norma Teresa, additional, Apolinário da Silva, Leandro, additional, Zaránd, Attila, additional, Ruiz-Bañobre, Juan, additional, Heuveline, Vincent, additional, Mecklin, Jukka-Pekka, additional, Pylvänäinen, Kirsi, additional, Renkonen-Sinisalo, Laura, additional, Lepistö, Anna, additional, Peltomäki, Päivi, additional, Therkildsen, Christina, additional, Madsen, Mia Gebauer, additional, Burgdorf, Stefan Kobbelgaard, additional, Hopper, John L., additional, Win, Aung Ko, additional, Haile, Robert W., additional, Lindor, Noralane, additional, Gallinger, Steven, additional, Le Marchand, Loïc, additional, Newcomb, Polly A., additional, Figueiredo, Jane, additional, Buchanan, Daniel D., additional, Thibodeau, Stephen N., additional, von Knebel Doeberitz, Magnus, additional, Loeffler, Markus, additional, Rahner, Nils, additional, Schröck, Evelin, additional, Steinke-Lange, Verena, additional, Schmiegel, Wolff, additional, Vangala, Deepak, additional, Perne, Claudia, additional, Hüneburg, Robert, additional, Redler, Silke, additional, Büttner, Reinhard, additional, Weitz, Jürgen, additional, Pineda, Marta, additional, Duenas, Nuria, additional, Vidal, Joan Brunet, additional, Moreira, Leticia, additional, Sánchez, Ariadna, additional, Hovig, Eivind, additional, Nakken, Sigve, additional, Green, Kate, additional, Lalloo, Fiona, additional, Hill, James, additional, Crosbie, Emma, additional, Mints, Miriam, additional, Goldberg, Yael, additional, Tjandra, Douglas, additional, ten Broeke, Sanne W., additional, Kariv, Revital, additional, Rosner, Guy, additional, Advani, Suresh H., additional, Thomas, Lidiya, additional, Shah, Pankaj, additional, Shah, Mithun, additional, Neffa, Florencia, additional, Esperon, Patricia, additional, Pavicic, Walter, additional, Torrezan, Giovana Tardin, additional, Bassaneze, Thiago, additional, Martin, Claudia Alejandra, additional, Moslein, Gabriela, additional, and Moller, Pål, additional

Published
2023
Full Text
View/download PDF

33. Supplementary Figure from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Author

Seppälä, Toni T., primary, Zimmerman, Jacquelyn W., primary, Suri, Reecha, primary, Zlomke, Haley, primary, Ivey, Gabriel D., primary, Szabolcs, Annamaria, primary, Shubert, Christopher R., primary, Cameron, John L., primary, Burns, William R., primary, Lafaro, Kelly J., primary, He, Jin, primary, Wolfgang, Christopher L., primary, Zou, Ying S., primary, Zheng, Lei, primary, Tuveson, David A., primary, Eshlemann, James R., primary, Ryan, David P., primary, Kimmelman, Alec C., primary, Hong, Theodore S., primary, Ting, David T., primary, Jaffee, Elizabeth M., primary, and Burkhart, Richard A., primary

Published
2023
Full Text
View/download PDF

34. Supplementary Table from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Author

Seppälä, Toni T., primary, Zimmerman, Jacquelyn W., primary, Suri, Reecha, primary, Zlomke, Haley, primary, Ivey, Gabriel D., primary, Szabolcs, Annamaria, primary, Shubert, Christopher R., primary, Cameron, John L., primary, Burns, William R., primary, Lafaro, Kelly J., primary, He, Jin, primary, Wolfgang, Christopher L., primary, Zou, Ying S., primary, Zheng, Lei, primary, Tuveson, David A., primary, Eshlemann, James R., primary, Ryan, David P., primary, Kimmelman, Alec C., primary, Hong, Theodore S., primary, Ting, David T., primary, Jaffee, Elizabeth M., primary, and Burkhart, Richard A., primary

Published
2023
Full Text
View/download PDF

35. Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Author

Seppälä, Toni T., primary, Zimmerman, Jacquelyn W., primary, Suri, Reecha, primary, Zlomke, Haley, primary, Ivey, Gabriel D., primary, Szabolcs, Annamaria, primary, Shubert, Christopher R., primary, Cameron, John L., primary, Burns, William R., primary, Lafaro, Kelly J., primary, He, Jin, primary, Wolfgang, Christopher L., primary, Zou, Ying S., primary, Zheng, Lei, primary, Tuveson, David A., primary, Eshlemann, James R., primary, Ryan, David P., primary, Kimmelman, Alec C., primary, Hong, Theodore S., primary, Ting, David T., primary, Jaffee, Elizabeth M., primary, and Burkhart, Richard A., primary

Published
2023
Full Text
View/download PDF

36. Supplementary Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Author

Seppälä, Toni T., primary, Zimmerman, Jacquelyn W., primary, Suri, Reecha, primary, Zlomke, Haley, primary, Ivey, Gabriel D., primary, Szabolcs, Annamaria, primary, Shubert, Christopher R., primary, Cameron, John L., primary, Burns, William R., primary, Lafaro, Kelly J., primary, He, Jin, primary, Wolfgang, Christopher L., primary, Zou, Ying S., primary, Zheng, Lei, primary, Tuveson, David A., primary, Eshlemann, James R., primary, Ryan, David P., primary, Kimmelman, Alec C., primary, Hong, Theodore S., primary, Ting, David T., primary, Jaffee, Elizabeth M., primary, and Burkhart, Richard A., primary

Published
2023
Full Text
View/download PDF

37. Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity

Author

Kansikas, Minttu, primary, Vähätalo, Laura, additional, Kantelinen, Jukka, additional, Kasela, Mariann, additional, Putula, Jaana, additional, Døhlen, Anni, additional, Paloviita, Pauliina, additional, Kärkkäinen, Emmi, additional, Lahti, Niklas, additional, Arnez, Philippe, additional, Kilpinen, Sami, additional, Alcala-Repo, Beatriz, additional, Pylvänäinen, Kirsi, additional, Pöyhönen, Minna, additional, Peltomäki, Päivi, additional, Järvinen, Heikki J., additional, Seppälä, Toni T., additional, Renkonen-Sinisalo, Laura, additional, Lepistö, Anna, additional, Mecklin, Jukka-Pekka, additional, and Nyström, Minna, additional

Published
2023
Full Text
View/download PDF

38. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Author

Cavestro, Giulia Martina, primary, Mannucci, Alessandro, additional, Balaguer, Francesc, additional, Hampel, Heather, additional, Kupfer, Sonia S., additional, Repici, Alessandro, additional, Sartore-Bianchi, Andrea, additional, Seppälä, Toni T., additional, Valentini, Vincenzo, additional, Boland, Clement Richard, additional, Brand, Randall E., additional, Buffart, Tineke E., additional, Burke, Carol A., additional, Caccialanza, Riccardo, additional, Cannizzaro, Renato, additional, Cascinu, Stefano, additional, Cercek, Andrea, additional, Crosbie, Emma J., additional, Danese, Silvio, additional, Dekker, Evelien, additional, Daca-Alvarez, Maria, additional, Deni, Francesco, additional, Dominguez-Valentin, Mev, additional, Eng, Cathy, additional, Goel, Ajay, additional, Guillem, Josè G., additional, Houwen, Britt B.S.L., additional, Kahi, Charles, additional, Kalady, Matthew F., additional, Kastrinos, Fay, additional, Kühn, Florian, additional, Laghi, Luigi, additional, Latchford, Andrew, additional, Liska, David, additional, Lynch, Patrick, additional, Malesci, Alberto, additional, Mauri, Gianluca, additional, Meldolesi, Elisa, additional, Møller, Pål, additional, Monahan, Kevin J., additional, Möslein, Gabriela, additional, Murphy, Caitlin C., additional, Nass, Karlijn, additional, Ng, Kimmie, additional, Oliani, Cristina, additional, Papaleo, Enrico, additional, Patel, Swati G., additional, Puzzono, Marta, additional, Remo, Andrea, additional, Ricciardiello, Luigi, additional, Ripamonti, Carla Ida, additional, Siena, Salvatore, additional, Singh, Satish K., additional, Stadler, Zsofia K., additional, Stanich, Peter P., additional, Syngal, Sapna, additional, Turi, Stefano, additional, Urso, Emanuele Damiano, additional, Valle, Laura, additional, Vanni, Valeria Stella, additional, Vilar, Eduardo, additional, Vitellaro, Marco, additional, You, Yi-Qian Nancy, additional, Yurgelun, Matthew B., additional, Zuppardo, Raffaella Alessia, additional, and Stoffel, Elena M., additional

Published
2023
Full Text
View/download PDF

40. The prognostic role of tumor budding and tumor-stroma ratio in pulmonary metastasis of colorectal carcinoma

Author

Karjula, Topias, primary, Kemi, Niko, additional, Niskakangas, Anne, additional, Mustonen, Olli, additional, Puro, Iiris, additional, Pohjanen, Vesa-Matti, additional, Kuopio, Teijo, additional, Elomaa, Hanna, additional, Ahtiainen, Maarit, additional, Mecklin, Jukka-Pekka, additional, Seppälä, Toni T., additional, Wirta, Erkki-Ville, additional, Sihvo, Eero, additional, Väyrynen, Juha P., additional, Yannopoulos, Fredrik, additional, and Helminen, Olli, additional

Published
2023
Full Text
View/download PDF

41. Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment:a report from the prospective Lynch syndrome database

Author

Dominguez-Valentin, Mev, Haupt, Saskia, Seppälä, Toni T., Sampson, Julian R., Sunde, Lone, Bernstein, Inge, Jenkins, Mark A., Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Balaguer, Francesc, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Dębniak, Tadeusz, Fruscio, Robert, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Katz, Lior H., Laish, Ido, Vainer, Elez, Vaccaro, Carlos, Carraro, Dirce Maria, Monahan, Kevin, Half, Elizabeth, Stakelum, Aine, Winter, Des, Kennelly, Rory, Gluck, Nathan, Sheth, Harsh, Abu-Freha, Naim, Greenblatt, Marc, Rossi, Benedito Mauro, Bohorquez, Mabel, Cavestro, Giulia Martina, Lino-Silva, Leonardo S., Horisberger, Karoline, Tibiletti, Maria Grazia, Nascimento, Ivana do, Thomas, Huw, Rossi, Norma Teresa, Apolinário da Silva, Leandro, Zaránd, Attila, Ruiz-Bañobre, Juan, Heuveline, Vincent, Mecklin, Jukka Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Peltomäki, Päivi, Therkildsen, Christina, Madsen, Mia Gebauer, Burgdorf, Stefan Kobbelgaard, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Schröck, Evelin, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, Redler, Silke, Büttner, Reinhard, Weitz, Jürgen, Pineda, Marta, Duenas, Nuria, Vidal, Joan Brunet, Moreira, Leticia, Sánchez, Ariadna, Hovig, Eivind, Nakken, Sigve, Green, Kate, Lalloo, Fiona, Hill, James, Crosbie, Emma, Mints, Miriam, Goldberg, Yael, Tjandra, Douglas, ten Broeke, Sanne W., Kariv, Revital, Rosner, Guy, Advani, Suresh H., Thomas, Lidiya, Shah, Pankaj, Shah, Mithun, Neffa, Florencia, Esperon, Patricia, Pavicic, Walter, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia Alejandra, Moslein, Gabriela, Moller, Pål, Dominguez-Valentin, Mev, Haupt, Saskia, Seppälä, Toni T., Sampson, Julian R., Sunde, Lone, Bernstein, Inge, Jenkins, Mark A., Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Balaguer, Francesc, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Dębniak, Tadeusz, Fruscio, Robert, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Katz, Lior H., Laish, Ido, Vainer, Elez, Vaccaro, Carlos, Carraro, Dirce Maria, Monahan, Kevin, Half, Elizabeth, Stakelum, Aine, Winter, Des, Kennelly, Rory, Gluck, Nathan, Sheth, Harsh, Abu-Freha, Naim, Greenblatt, Marc, Rossi, Benedito Mauro, Bohorquez, Mabel, Cavestro, Giulia Martina, Lino-Silva, Leonardo S., Horisberger, Karoline, Tibiletti, Maria Grazia, Nascimento, Ivana do, Thomas, Huw, Rossi, Norma Teresa, Apolinário da Silva, Leandro, Zaránd, Attila, Ruiz-Bañobre, Juan, Heuveline, Vincent, Mecklin, Jukka Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Peltomäki, Päivi, Therkildsen, Christina, Madsen, Mia Gebauer, Burgdorf, Stefan Kobbelgaard, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Schröck, Evelin, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, Redler, Silke, Büttner, Reinhard, Weitz, Jürgen, Pineda, Marta, Duenas, Nuria, Vidal, Joan Brunet, Moreira, Leticia, Sánchez, Ariadna, Hovig, Eivind, Nakken, Sigve, Green, Kate, Lalloo, Fiona, Hill, James, Crosbie, Emma, Mints, Miriam, Goldberg, Yael, Tjandra, Douglas, ten Broeke, Sanne W., Kariv, Revital, Rosner, Guy, Advani, Suresh H., Thomas, Lidiya, Shah, Pankaj, Shah, Mithun, Neffa, Florencia, Esperon, Patricia, Pavicic, Walter, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia Alejandra, Moslein, Gabriela, and Moller, Pål

Abstract

Background The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical ca, Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We ac

Published
2023

43. Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Author

Dominguez-Valentin, Mev, Seppälä, Toni T., Sampson, Julian R., Macrae, Finlay, Winship, Ingrid, Evans, D. Gareth, Scott, Rodney J., Burn, John, Möslein, Gabriela, Bernstein, Inge, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Lindblom, Annika, Plazzer, John-Paul, Tjandra, Douglas, Thomas, Huw, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Capella, Gabriel, Pineda, Marta, Navarro, Matilde, Vidal, Joan Brunet, Rønlund, Karina, Nielsen, Randi Thyregaard, Yilmaz, Mette, Elvang, Louise Laurberg, Katz, Lior, Nielsen, Maartje, ten Broeke, Sanne W., Nakken, Sigve, Hovig, Eivind, Sunde, Lone, Kloor, Matthias, Knebel Doeberitz, Magnus v, Ahadova, Aysel, Lindor, Noralane, Steinke-Lange, Verena, Holinski-Feder, Elke, Mecklin, Jukka-Pekka, and Møller, Pål

Published
2019
Full Text
View/download PDF

44. Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report

Author

Seppälä, Toni T., Ahadova, Aysel, Dominguez-Valentin, Mev, Macrae, Finlay, Evans, D. Gareth, Therkildsen, Christina, Sampson, Julian, Scott, Rodney, Burn, John, Möslein, Gabriela, Bernstein, Inge, Holinski-Feder, Elke, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Lautrup, Charlotte Kvist, Lindblom, Annika, Plazzer, John-Paul, Winship, Ingrid, Tjandra, Douglas, Katz, Lior H., Aretz, Stefan, Hüneburg, Robert, Holzapfel, Stefanie, Heinimann, Karl, Valle, Adriana Della, Neffa, Florencia, Gluck, Nathan, de Vos tot Nederveen Cappel, Wouter H., Vasen, Hans, Morak, Monika, Steinke-Lange, Verena, Engel, Christoph, Rahner, Nils, Schmiegel, Wolff, Vangala, Deepak, Thomas, Huw, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Capella, Gabriel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, ten Broeke, Sanne, Nielsen, Maartje, Ljungmann, Ken, Nakken, Sigve, Lindor, Noralane, Frayling, Ian, Hovig, Eivind, Sunde, Lone, Kloor, Matthias, Mecklin, Jukka-Pekka, Kalager, Mette, and Møller, Pål

Published
2019
Full Text
View/download PDF

46. CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

Author

Karjula, Topias, primary, Elomaa, Hanna, additional, Niskakangas, Anne, additional, Mustonen, Olli, additional, Puro, Iiris, additional, Kuopio, Teijo, additional, Ahtiainen, Maarit, additional, Mecklin, Jukka-Pekka, additional, Seppälä, Toni T., additional, Wirta, Erkki-Ville, additional, Sihvo, Eero, additional, Väyrynen, Juha P., additional, Yannopoulos, Fredrik, additional, and Helminen, Olli, additional

Published
2022
Full Text
View/download PDF

47. Systemic circulating microRNA landscape in Lynch syndrome

Author

Sievänen, Tero, primary, Korhonen, Tia‐Marje, additional, Jokela, Tiina, additional, Ahtiainen, Maarit, additional, Lahtinen, Laura, additional, Kuopio, Teijo, additional, Lepistö, Anna, additional, Sillanpää, Elina, additional, Mecklin, Jukka‐Pekka, additional, Seppälä, Toni T., additional, and Laakkonen, Eija K., additional

Published
2022
Full Text
View/download PDF

48. Clinical characteristics of pancreatic and biliary tract cancers in Lynch syndrome : A retrospective analysis from the Finnish National Lynch Syndrome Research Registry

Author

Zalevskaja, Kristina, Mecklin, Jukka Pekka, Seppälä, Toni T., ATG - Applied Tumor Genomics, HUS Abdominal Center, Tampere University, Clinical Medicine, and TAYS Cancer Centre

Subjects
Lynch syndrome (LS), Cancer Research, hereditary nonpolyposis colon cancer, microsatellite instability (MSI), 3122 Cancers, pancreatic cancer, Pancreatic cancer, 3121 Internal medicine, mikrosatelliitit, Lynch syndrome, Oncology, hereditary nonpolyposis colon cancer (HNPCC), biliary tract cancer, Biliary tract cancer, microsatellite instability, Lynchin oireyhtymä, haimasyöpä, paksusuolisyöpä
Abstract

IntroductionPatients with Lynch syndrome (LS) have an increased lifetime risk of pancreatic cancer (PC) and biliary tract cancer (BTC). These cancers have a notoriously pessimistic prognosis due to late diagnosis and limited therapeutic options. There are limited data based on small cohorts reviewing PC and BTC in LS patients.MethodsIn this retrospective study of the Lynch Syndrome Registry of Finland (LSRFi), records of genetically verified LS patients diagnosed with PC or BTC between 1982 and 2020 were analyzed.ResultsThirty-nine patients were included: tumor(s) were in the pancreas in 26 patients, in the biliary tract in 10, and in the ampulla of Vater in three. A pathogenic germline variant was found in MLH1 in 33 of 39 patients. Twenty-six patients with 28 tumors located in the pancreas were identified: 23 pancreatic ductal adenocarcinomas (PDACs) and five neuroendocrine tumors (NETs). The median age at diagnosis of PC was 64 years (range of 38–81). In PC, the 5-year overall survival (OS) rate was 20%, and in PDAC, it was 13.6%. Ten patients with BTC were diagnosed: two intrahepatic, five perihilar, two distal extrahepatic cholangiocarcinomas, and one gallbladder carcinoma. Eight patients were male, and the median age at diagnosis was 54 years (range of 34–82). The 5-year OS rate for BTC was 30%. Metachronous tumors were diagnosed in 28 patients (70%). Colorectal cancer was the most common metachronous tumor, diagnosed in 20 patients (51%), and diagnosed prior to PC or BTC in all cases. Curative surgery was attempted on 17 of 39 patients. For 30 patients (91%), the cause of death was PC or BTC; two patients died from another LS-associated cancer, and one died from a stroke.ConclusionAlthough the survival of LS patients with PC or BTC is better than in sporadic cancers, it is still poor and may be reflected by the relatively higher surgical resectability accounted for by the earlier age of onset. More studies on analyses of the molecular and immune profile, screening, and management of LS-associated pancreaticobiliary cancers are warranted.

Published
2023

49. Delphi initiative for early-onset colorectal cancer (DIRECt). International Management Guidelines

Author

Cavestro Giulia, M, Mannucci, A, Balaguer, F, Hampel, H, Kupfer, SS, Repici, A, Sartore-Bianchi, A, Seppälä Toni, T, Valentini, V, Boland Clement, R, Brand, RE, Buffart, TE, Burke, CA, Caccialanza, R, Cannizzaro, R, Cascinu, S, Cercek, A, Crosbie, EJ, Danese, S, Dekker, E, Daca-Alvarez, M, Deni, F, Dominguez-Valentin, M, Eng, C, Goel, A, Guillem Josè, G, Houwen, B, Kahi, C, Kalady, MF, Kastrinos, F, Kühn, F, Laghi, L, Latchford, A, Liska, D, Lynch, P, Malesci, A, Mauri, G, Meldolesi, E, Møller, P, Monahan, KJ, Moslein, G, Murphy, CC, Nass, K, Ng, K, Oliani, C, Papaleo, E, Patel, SG, Puzzono, M, Remo, A, Ricciardiello, L, Ripamonti Carla, I, Siena, S, Singh, SK, Stadler, ZK, Stanich, PP, Syngal, S, Turi, S, Urso Emanuele, D, Valle, L, Vanni Valeria, S, Vilar, E, Vitellaro, M, You, Y-QN, Yurgelun, MB, Zuppardo Raffaella, A, Stoffel, EM, Associazione Italiana Familiarità Ereditarietà Tumori, Collaborative Group of the Americas on Inherited Gastrointestinal Cancers, European Hereditary Tumor Group, International Society for Gastrointestinal Hereditary Tumours, Tampere University, Clinical Medicine, Department of Gastroenterology, Gastroenterology and Hepatology, CCA - Cancer Treatment and Quality of Life, CCA - Imaging and biomarkers, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, and Internal medicine

Subjects
Colorectal Cancer, 50 Years, Clinical, Hepatology, Settore MED/06 - Oncologia Medica, 3122 Cancers, Gastroenterology, Young, Recommendation
Abstract

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC. publishedVersion

Published
2022

50. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

Author

Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John-Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka-Pekka, Nielsen, Maartje, and Møller, Pål

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results