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1. Distant metastasis after treatment of pT1 colorectal carcinomas

Author

Gijsbers, K., additional, van der Schee, L., additional, Backes, Y., additional, Tuynman, J., additional, Alderlieste, Y., additional, Bosman, J., additional, Van Berkel, A., additional, Boersma, F., additional, Boonstra, J., additional, Bos, P., additional, Didden, P., additional, Groen, J. N., additional, Kessels, K., additional, Van Lent, A.U. G., additional, Mundt, M. W., additional, Schrauwen, R.W. M., additional, Schreuder, R. M., additional, Schwartz, M. P., additional, Seerden, T., additional, Groenen, M.J. M., additional, Droste, J. Terhaar Sive, additional, Vogelaar, L., additional, De Vos Tot Nederveen Cappel, W. H., additional, Van Westreenen, H. L., additional, Wolfhagen, F., additional, Vink, G. R., additional, Koopman, M., additional, Vleggaar, F., additional, Elias, S., additional, Lacle, M., additional, Ter Borg, F., additional, and Moons, L.M. G., additional

Published
2024
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5. Standardizing training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicenter, cluster randomized trial

Author

Meulen, L.W. T., additional, Bogie, R.M. M., additional, Siersema, P. D., additional, Winkens, B., additional, Vlug, M., additional, Wolfhagen, F., additional, Baven-Pronk, M., additional, Van Der Voorn, M., additional, Schwartz, M. P., additional, Vogelaar, L., additional, De Vos Tot Nederveen Cappel, W. H., additional, Seerden, T., additional, Hazen, W. L., additional, Schrauwen, R.W. M., additional, Herrero, L. Alvarez, additional, Schreuder, R. M., additional, Van Nunen, A. B., additional, Stoop, E., additional, De Bruin, G. J., additional, Bos, P., additional, Marsman, W. A., additional, Kuiper, E., additional, De Bièvre, M., additional, Alderlieste, Y., additional, Roomer, R., additional, Groen, J. N., additional, Bigirwamungu-Bargeman, M., additional, Van Leerdam, M., additional, Roberts-Bos, L., additional, Boersma, F., additional, Thurnau, K., additional, De Vries, R. S., additional, Ramaker, J. M., additional, De Ridder, R.J. J., additional, Pellisé, M., additional, Bourke, M. J., additional, Masclee, A.A. M., additional, and Moons, L.M. G., additional

Published
2023
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9. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (Genetics in Medicine, (2020), 22, 1, (15-25), 10.1038/s41436-019-0596-9)

Author

Dominguez-Valentin M., Sampson J. R., Seppala T. T., ten Broeke S. W., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Della Valle A., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., Knebel Doeberitz M., Loeffler M., Rahner N., Schackert H. K., Steinke-Lange V., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Wadt K., Therkildsen C., Okkels H., Ketabi Z., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Frayling I. M., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Nielsen M., Moller P., Dominguez-Valentin, M., Sampson, J. R., Seppala, T. T., ten Broeke, S. W., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Della Valle, A., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., Knebel Doeberitz, M., Loeffler, M., Rahner, N., Schackert, H. K., Steinke-Lange, V., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Wadt, K., Therkildsen, C., Okkels, H., Ketabi, Z., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Frayling, I. M., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., Mecklin, J. -P., Nielsen, M., and Moller, P.

Abstract

The original version of this Article did not contain details of Dutch Cancer Society (DCS) funding (grant number UL 2017-8223) in the Acknowledgements section. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2020

11. Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum

Author

Dominguez-Valentin M., Sampson J. R., Moller P., Seppala T. T., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., Nielsen M., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Valle A. D., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., von Knebel Doeberitz M., Loeffler M., Rahner N., Weitz J., Steinke-Lange V., ten Broeke S. W., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Jensen L. H., Madsen M. B., Kroldrup L., Nilbert M., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Vidal J. B., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Dominguez-Valentin, M., Sampson, J. R., Moller, P., Seppala, T. T., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., Nielsen, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Valle, A. D., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., von Knebel Doeberitz, M., Loeffler, M., Rahner, N., Weitz, J., Steinke-Lange, V., ten Broeke, S. W., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Jensen, L. H., Madsen, M. B., Kroldrup, L., Nilbert, M., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Vidal, J. B., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., and Mecklin, J. -P.

Subjects
Male, Adult, Oncology, Cancer Research, 2019-20 coronavirus outbreak, medicine.medical_specialty, sarcoma, Databases, Factual, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sarcoma/diagnosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Aged, business.industry, Sarcoma, Syndrome, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, MSH2, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Female, 030211 gastroenterology & hepatology, business
Published
2020
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12. High detection rate of adenomas in familial colorectal cancer

Author

van der Meulen-de Jong, A E, Morreau, H, Becx, M C J M, Crobach, L F S J, Haastert, M van, Hove, W R ten, Kleibeuker, J H, Meijssen, M A C, Nagengast, F M, Rijk, M C M, Salemans, J M J I, Stronkhorst, A, Tuynman, H A R E, Vecht, J, Verhulst, M L, de Vos tot Nederveen Cappel, W H, Walinga, H, Weinhardt, O K, Westerveld, B D, Witte, A M C, Wolters, H J, and Vasen, H F A

Published
2011
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13. Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy

Author

Huisman, J. F., primary, Schoenaker, I. J. H., additional, Brohet, R. M., additional, Reerink, O., additional, van der Sluis, H., additional, Moll, F. C. P., additional, de Boer, E., additional, de Graaf, J. C., additional, de Vos tot Nederveen Cappel, W. H., additional, Beets, G. L., additional, and van Westreenen, H. L., additional

Published
2020
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20. Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes

Author

Overwater, A., Kessels, K., Elias, S. G., Backes, Y., Spanier, B. W M, Seerden, T. C J, Pullens, H. J M, de Vos tot Nederveen Cappel, W. H., van den Blink, A., Offerhaus, G. J A, van Bergeijk, J., Kerkhof, M., Geesing, J. M J, Groen, J. N., van Lelyveld, N., ter Borg, F., Wolfhagen, F., Siersema, P. D., Lacle, M. M., Moons, L. M G, Overwater, A., Kessels, K., Elias, S. G., Backes, Y., Spanier, B. W M, Seerden, T. C J, Pullens, H. J M, de Vos tot Nederveen Cappel, W. H., van den Blink, A., Offerhaus, G. J A, van Bergeijk, J., Kerkhof, M., Geesing, J. M J, Groen, J. N., van Lelyveld, N., ter Borg, F., Wolfhagen, F., Siersema, P. D., Lacle, M. M., and Moons, L. M G

Published
2018

21. Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes

Author

MS MDL 1, Epi Kanker Team A, JC onderzoeksprogramma Kanker, Cancer, Pathologie Pathologen staf, MS MDL Oncologie, Overwater, A., Kessels, K., Elias, S. G., Backes, Y., Spanier, B. W M, Seerden, T. C J, Pullens, H. J M, de Vos tot Nederveen Cappel, W. H., van den Blink, A., Offerhaus, G. J A, van Bergeijk, J., Kerkhof, M., Geesing, J. M J, Groen, J. N., van Lelyveld, N., ter Borg, F., Wolfhagen, F., Siersema, P. D., Lacle, M. M., Moons, L. M G, MS MDL 1, Epi Kanker Team A, JC onderzoeksprogramma Kanker, Cancer, Pathologie Pathologen staf, MS MDL Oncologie, Overwater, A., Kessels, K., Elias, S. G., Backes, Y., Spanier, B. W M, Seerden, T. C J, Pullens, H. J M, de Vos tot Nederveen Cappel, W. H., van den Blink, A., Offerhaus, G. J A, van Bergeijk, J., Kerkhof, M., Geesing, J. M J, Groen, J. N., van Lelyveld, N., ter Borg, F., Wolfhagen, F., Siersema, P. D., Lacle, M. M., and Moons, L. M G

Published
2018

23. Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer : A Multicenter Cohort Study

Author

Backes, Y, de Vos Tot Nederveen Cappel, W H, van Bergeijk, J, Ter Borg, F, Schwartz, M P, Spanier, B W M, Geesing, J M J, Kessels, K, Kerkhof, M, Groen, J N, Wolfhagen, F H J, Seerden, T C J, van Lelyveld, N, Offerhaus, G J A, Siersema, P D, Lacle, M M, Moons, L M G, Backes, Y, de Vos Tot Nederveen Cappel, W H, van Bergeijk, J, Ter Borg, F, Schwartz, M P, Spanier, B W M, Geesing, J M J, Kessels, K, Kerkhof, M, Groen, J N, Wolfhagen, F H J, Seerden, T C J, van Lelyveld, N, Offerhaus, G J A, Siersema, P D, Lacle, M M, and Moons, L M G

Published
2017

24. Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study

Author

MS MDL 1, Cancer, MS CGO, Pathologie Pathologen staf, MS MDL Oncologie, Backes, Y, de Vos Tot Nederveen Cappel, W H, van Bergeijk, J, Ter Borg, F, Schwartz, M P, Spanier, B W M, Geesing, J M J, Kessels, K, Kerkhof, M, Groen, J N, Wolfhagen, F H J, Seerden, T C J, van Lelyveld, N, Offerhaus, G J A, Siersema, P D, Lacle, M M, Moons, L M G, MS MDL 1, Cancer, MS CGO, Pathologie Pathologen staf, MS MDL Oncologie, Backes, Y, de Vos Tot Nederveen Cappel, W H, van Bergeijk, J, Ter Borg, F, Schwartz, M P, Spanier, B W M, Geesing, J M J, Kessels, K, Kerkhof, M, Groen, J N, Wolfhagen, F H J, Seerden, T C J, van Lelyveld, N, Offerhaus, G J A, Siersema, P D, Lacle, M M, and Moons, L M G

Published
2017

26. Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study

Author

Backes, Y, primary, de Vos tot Nederveen Cappel, W H, additional, van Bergeijk, J, additional, ter Borg, F, additional, Schwartz, M P, additional, Spanier, B W M, additional, Geesing, J M J, additional, Kessels, K, additional, Kerkhof, M, additional, Groen, J N, additional, Wolfhagen, F H J, additional, Seerden, T C J, additional, van Lelyveld, N, additional, Offerhaus, G J A, additional, Siersema, P D, additional, Lacle, M M, additional, and Moons, L M G, additional

Published
2017
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27. Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial) : Rationale and design of a multicenter randomized clinical trial

Author

Backes, Y., Moons, L. M G, van Bergeijk, J. D., Berk, L., ter Borg, F., ter Borg, P. C J, Elias, S. G., Geesing, J. M J, Groen, J. N., Hadithi, M., Hardwick, J. C H, Kerkhof, M., Mangen, M. J J, Straathof, J. W A, Schröder, R., Schwartz, M. P., Spanier, B. W M, de Vos tot Nederveen Cappel, W. H., Wolfhagen, F. H J, Koch, A. D., Backes, Y., Moons, L. M G, van Bergeijk, J. D., Berk, L., ter Borg, F., ter Borg, P. C J, Elias, S. G., Geesing, J. M J, Groen, J. N., Hadithi, M., Hardwick, J. C H, Kerkhof, M., Mangen, M. J J, Straathof, J. W A, Schröder, R., Schwartz, M. P., Spanier, B. W M, de Vos tot Nederveen Cappel, W. H., Wolfhagen, F. H J, and Koch, A. D.

Published
2016

28. Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Author

MS MDL 1, Cancer, MS MDL Oncologie, Epi Kanker Team A, JC onderzoeksprogramma Kanker, HTA Onderzoek Team 1, JC onderzoeksprogramma Infectieziekten, Circulatory Health, JC onderzoeksprogramma Methodologie, Backes, Y., Moons, L. M G, van Bergeijk, J. D., Berk, L., ter Borg, F., ter Borg, P. C J, Elias, S. G., Geesing, J. M J, Groen, J. N., Hadithi, M., Hardwick, J. C H, Kerkhof, M., Mangen, M. J J, Straathof, J. W A, Schröder, R., Schwartz, M. P., Spanier, B. W M, de Vos tot Nederveen Cappel, W. H., Wolfhagen, F. H J, Koch, A. D., MS MDL 1, Cancer, MS MDL Oncologie, Epi Kanker Team A, JC onderzoeksprogramma Kanker, HTA Onderzoek Team 1, JC onderzoeksprogramma Infectieziekten, Circulatory Health, JC onderzoeksprogramma Methodologie, Backes, Y., Moons, L. M G, van Bergeijk, J. D., Berk, L., ter Borg, F., ter Borg, P. C J, Elias, S. G., Geesing, J. M J, Groen, J. N., Hadithi, M., Hardwick, J. C H, Kerkhof, M., Mangen, M. J J, Straathof, J. W A, Schröder, R., Schwartz, M. P., Spanier, B. W M, de Vos tot Nederveen Cappel, W. H., Wolfhagen, F. H J, and Koch, A. D.

Published
2016

29. Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes

Author

Overwater, A, primary, Kessels, K, additional, Elias, S G, additional, Backes, Y, additional, Spanier, B W M, additional, Seerden, T C J, additional, Pullens, H J M, additional, de Vos tot Nederveen Cappel, W H, additional, van den Blink, A, additional, Offerhaus, G J A, additional, van Bergeijk, J, additional, Kerkhof, M, additional, Geesing, J M J, additional, Groen, J N, additional, van Lelyveld, N, additional, ter Borg, F, additional, Wolfhagen, F, additional, Siersema, P D, additional, Lacle, M M, additional, and Moons, L M G, additional

Published
2016
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30. Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): rationale and design of a multicenter randomized clinical trial

Author

Backes, Y., primary, Moons, L. M. G., additional, van Bergeijk, J. D., additional, Berk, L., additional, ter Borg, F., additional, ter Borg, P. C. J., additional, Elias, S. G., additional, Geesing, J. M. J., additional, Groen, J. N., additional, Hadithi, M., additional, Hardwick, J. C. H., additional, Kerkhof, M., additional, Mangen, M. J. J., additional, Straathof, J. W. A., additional, Schröder, R., additional, Schwartz, M. P., additional, Spanier, B. W. M., additional, de Vos tot Nederveen Cappel, W. H., additional, Wolfhagen, F. H. J., additional, and Koch, A. D., additional

Published
2016
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31. Consequences of testing for mismatch repair deficiency of colorectal cancer in clinical practice.

Author

Leicher, L. W., Lammertink, M. H. A., Offerman, S. R., Morreau, H., De Jong, M. M., De Groot, J. W. B., Van Westreenen, H. L., Vasen, H. F. A., and De Vos Tot Nederveen Cappel, W. H.

Subjects
HEREDITARY nonpolyposis colorectal cancer, DNA mismatch repair, COLON cancer treatment, PATIENTS
Abstract

Introduction: Mismatch repair deficiency (dMMR) can be found in Lynch syndrome (LS)-associated colorectal carcinoma and in 15% of sporadic colorectal cancer (CRC). Outcome of MMR-deficiency testing is important for surgical decisions as extended colectomy is recommended in young LS-patients with CRC. Moreover, the finding of a dMMR tumour has consequences for the choices of adjuvant chemotherapy as MMR-deficient CRC is resistant to 5-fluorouracil (5-FU) monotherapy. Aims of our study are to evaluate whether MMR-deficiency testing leads to (1) identification of LS, (2) change in surgical treatment and (3) adjustment of systemic therapy in patients with dMMR CRC. Methods: We performed a multicentre, retrospective study, in a community hospital and a University Medical Centre. We included all CRC-patients between 2012 and 2016 who were tested for microsatellite instability. We collected clinical data such as gender, age, referral to clinical geneticist, surgical procedure and choice of chemotherapy. Results: We analysed 225 CRCs. Twenty-four (10.7%) of 225 CRC were MMR-deficient. Of the 24 patients with dMMR CRC, 18 (75%) were referred to the clinical geneticist and in nine (37%) patients a MMR mutation was identified. In one (4%) of the 24 patients, a subtotal colectomy was performed. In seven (35%) out of 20 MMR deficient patients, the chemotherapy regimen was adjusted. Conclusions: The finding of a dMMR CRC had consequences for decisions on chemotherapy in a relative high proportion of patients. We recommend testing in all patients with CRC independent of age at diagnosis, as proper treatment decisions and genetic counselling are very important. [ABSTRACT FROM AUTHOR]

Published
2018
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32. Consequence of Restaging After Neoadjuvant Treatment for Locally Advanced Rectal Cancer

Author

Bisschop, C., primary, Tjalma, J. J. J., additional, Hospers, G. A. P., additional, Van Geldere, D., additional, de Groot, J. W. B., additional, Wiegman, E. M., additional, Van’t Veer-ten Kate, M., additional, Havenith, M. G., additional, Vecht, J., additional, Beukema, J. C., additional, Kats-Ugurlu, G., additional, Mahesh, S. V. K., additional, van Etten, B., additional, Havenga, K., additional, Burgerhof, J. G. M., additional, de Groot, D. J. A., additional, and de Vos tot Nederveen Cappel, W. H., additional

Published
2014
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33. High detection rate of adenomas in familial colorectal cancer

Author

van der Meulen-de Jong, A. E., primary, Morreau, H., additional, Becx, M. C. J. M., additional, Crobach, L. F. S. J., additional, Haastert, M. v., additional, Hove, W. R. t., additional, Kleibeuker, J. H., additional, Meijssen, M. A. C., additional, Nagengast, F. M., additional, Rijk, M. C. M., additional, Salemans, J. M. J. I., additional, Stronkhorst, A., additional, Tuynman, H. A. R. E., additional, Vecht, J., additional, Verhulst, M. L., additional, de Vos tot Nederveen Cappel, W. H., additional, Walinga, H., additional, Weinhardt, O. K., additional, Westerveld, B. D., additional, Witte, A. M. C., additional, Wolters, H. J., additional, and Vasen, H. F. A., additional

Published
2010
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34. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

Author

Guy Rosner, Walter Hernán Pavicic, Claudia Perne, Carlos A. Vaccaro, Elke Holinski-Feder, Leticia Moreira, Wouter H. de Vos tot Nederveen Cappel, Stefan Aretz, Einar Andreas Rødland, Polly A. Newcomb, Karin Alvarez, Ariadna Sánchez, Lone Sunde, Wolff Schmiegel, Joan Brunet, Marc S. Greenblatt, Christina Therkildsen, Karl Heinimann, Lior H. Katz, Fiona Lalloo, Jürgen Weitz, Anna Lepistö, Rolf H. Sijmons, Maartje Nielsen, Hans F. A. Vasen, Deepak Vangala, Monika Morak, Jukka-Pekka Mecklin, Toni T. Seppälä, Sigve Nakken, Stefanie Holzapfel, Douglas Tjandra, Finlay A. Macrae, Päivi Peltomäki, Daniel D. Buchanan, Stephen N. Thibodeau, Adriana Della Valle, James Hill, Annika Lindblom, Bernardo Bonanni, Reinhard Büttner, Francisco López-Köstner, Giulia Martina Cavestro, John Burn, Emma J Crosbie, Lucio Bertario, Sanne W. ten Broeke, D. G. R. Evans, Kate Green, Verena Steinke-Lange, Eivind Hovig, Miquel Serra-Burriel, Francesc Balaguer, Kirsi Pylvänäinen, Gabriela Möslein, Revital Kariv, Thomas Hansen, Maria Grazia Tibiletti, Tamara Alejandra Piñero, Nils Rahner, Magnus von Knebel Doeberitz, Ingrid Winship, Nathan Gluck, Lars Joachim Lindberg, Christoph Engel, Mev Dominguez-Valentin, John-Paul Plazzer, Julian R. Sampson, Marta Pineda, John L. Hopper, Pablo Kalfayan, Heike Görgens, Aung Ko Win, Steven Gallinger, Loic Le Marchand, Mark A. Jenkins, Markus Loeffler, Noralane M. Lindor, Inge Bernstein, Pål Møller, Laura Renkonen-Sinisalo, Florencia Neffa, Huw Thomas, Gabriel Capellá, Jane C. Figueiredo, Miriam Mints, Patricia Esperon, Matilde Navarro, Robert Hüneburg, Guided Treatment in Optimal Selected Cancer Patients (GUTS), HUS Abdominal Center, Department of Surgery, Genome-Scale Biology (GSB) Research Program, II kirurgian klinikka, ATG - Applied Tumor Genomics, Research Programs Unit, Clinicum, Department of Medical and Clinical Genetics, Dominguez-Valentin, M., Plazzer, J. -P., Sampson, J. R., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Macrae, F., Winship, I. M., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Nielsen, M., Bertario, L., Bonanni, B., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Della Valle, A., Lopez-Kostner, F., Alvarez, K., Gluck, N., Katz, L., Heinimann, K., Vaccaro, C. A., Nakken, S., Hovig, E., Green, K., Lalloo, F., Hill, J., Vasen, H. F. A., Perne, C., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., Doeberitz, M. V. K., Loeffler, M., Rahner, N., Weitz, J., Steinke-Lange, V., Schmiegel, W., Vangala, D., Crosbie, E. J., Pineda, M., Navarro, M., Brunet, J., Moreira, L., Sanchez, A., Serra-Burriel, M., Mints, M., Kariv, R., Rosner, G., Pinero, T. A., Pavicic, W. H., Kalfayan, P., Ten Broeke, S. W., Mecklin, J. -P., Pylvanainen, K., Renkonen-Sinisalo, L., Lepisto, A., Peltomaki, P., Hopper, J. L., Win, A. K., Buchanan, D. D., Lindor, N. M., Gallinger, S., Marchand, L. L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Therkildsen, C., Hansen, T. V. O., Lindberg, L., Rodland, E. A., Neffa, F., Esperon, P., Tjandra, D., Moslein, G., Seppala, T. T., and Moller, P.

Subjects
cancer incidence, 0302 clinical medicine, Malalties hereditàries, Missense mutation, 8Q23.3, Càncer, Cancer, Genetics, 0303 health sciences, medicine.diagnostic_test, Factors de risc en les malalties, MISMATCH REPAIR GENES, MLH1, General Medicine, Penetrance, Lynch syndrome, 3. Good health, syöpägeenit, 030220 oncology & carcinogenesis, Medicine, syöpätaudit, ilmaantuvuus, Genetic diseases, congenital, hereditary, and neonatal diseases and abnormalities, missense, 11Q23.1, Risk factors in diseases, CANCER-RISK, Article, aberrant splicing, 03 medical and health sciences, AGE, medicine, Genetic predisposition, ddc:610, MSH2, Lynchin oireyhtymä, penetrance, 030304 developmental biology, Genetic testing, truncating, perinnölliset taudit, business.industry, MUTATIONS, HMSH2, nutritional and metabolic diseases, medicine.disease, digestive system diseases, 3121 General medicine, internal medicine and other clinical medicine, business
Abstract

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Published
2021
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35. Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants:a Prospective Lynch Syndrome Database report

Author

Einar Andreas Rødland, Joan B. Vida, Heike Görgens, Eivind Hovig, Kirsi Pylvänäinen, Monika Morak, Wouter H. de Vos tot Nederveen Cappel, Lone Sunde, Mark A. Jenkins, Lucio Bertario, Patricia Esperon, Reinhard Büttner, Finlay A. Macrae, Inge Bernstein, Marc S. Greenblatt, Wolff Schmiegel, Giulia Martina Cavestro, Maria Grazia Tibiletti, Silke Redler, Zohreh Ketabi, Karl Heinimann, Fiona Lalloo, Huw Thomas, Christina Therkildsen, Deepak Vangala, Magnus von Knebel Doeberitz, Matilde Navarro, Erik Rokkones, Douglas Tjandra, D. G. Evans, Marta Pineda, Marian J.E. Mourits, Lior H. Katz, Bernardo Bonanni, Pablo Kalfayan, Stephen N. Thibodeau, Loic Le Marchand, Revital Kariv, Maartje Nielsen, Emma J Crosbie, Oliver G. Denton, Stefanie Holzapfel, Guy Rosner, Mev Dominguez-Valentin, John Burn, Verena Steinke-Lange, Carlos A. Vaccaro, Gabriela Möslein, Elke Holinski-Feder, Gabriel Capellá, Johanna Tecklenburg, Karin Wadt, Kate Green, Christoph Engel, Miriam Mints, Anna Lepistö, Tamara Alejandra Piñero, Jukka-Pekka Mecklin, John L. Hopper, Robert Hüneburg, Markus Loeffler, Florencia Neffa, Toni T. Seppälä, Claudia Perne, Polly A. Newcomb, Karin Alvarez, Adriana Della Valle, Julian R. Sampson, Sanne W. ten Broeke, Francisco Lopez-Koestner, John-Paul Plazzer, James Hill, Hans Georg Strauß, Ingrid Winship, Nathan Gluck, Aung Ko Win, Jane C. Figueiredo, Jürgen Weitz, Hans F. A. Vasen, Rolf H. Sijmons, Walter Hernán Pavicic, Stefan Aretz, Steven Gallinger, Noralane M. Lindor, Pål Møller, Laura Renkonen-Sinisalo, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Seppala, T. T., Dominguez-Valentin, M., Crosbie, E. J., Engel, C., Aretz, S., Macrae, F., Winship, I., Capella, G., Thomas, H., Hovig, E., Nielsen, M., Sijmons, R. H., Bertario, L., Bonanni, B., Tibiletti, M. G., Cavestro, G. M., Mints, M., Gluck, N., Katz, L., Heinimann, K., Vaccaro, C. A., Green, K., Lalloo, F., Hill, J., Schmiegel, W., Vangala, D., Perne, C., Strauss, H. -G., Tecklenburg, J., Holinski-Feder, E., Steinke-Lange, V., Mecklin, J. -P., Plazzer, J. -P., Pineda, M., Navarro, M., Vida, J. B., Kariv, R., Rosner, G., Pinero, T. A., Pavicic, W., Kalfayan, P., ten Broeke, S. W., Jenkins, M. A., Sunde, L., Bernstein, I., Burn, J., Greenblatt, M., de Vos tot Nederveen Cappel, W. H., Della Valle, A., Lopez-Koestner, F., Alvarez, K., Buttner, R., Gorgens, H., Morak, M., Holzapfel, S., Huneburg, R., von Knebel Doeberitz, M., Loeffler, M., Redler, S., Weitz, J., Pylvanainen, K., Renkonen-Sinisalo, L., Lepisto, A., Hopper, J. L., Win, A. K., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Therkildsen, C., Wadt, K. A. W., Mourits, M. J. E., Ketabi, Z., Denton, O. G., Rodland, E. A., Vasen, H., Neffa, F., Esperon, P., Tjandra, D., Moslein, G., Rokkones, E., Sampson, J. R., Evans, D. G., Moller, P., Genome-Scale Biology (GSB) Research Program, HUS Abdominal Center, Clinicum, II kirurgian klinikka, Department of Surgery, and Doctoral Programme in Clinical Research

Subjects
0301 basic medicine, Cancer Research, Oophorectomy, Databases, Factual, Colorectal cancer, SURGERY, medicine.medical_treatment, Càncer d'ovari, computer.software_genre, DNA Mismatch Repair, 0302 clinical medicine, Endometrial cancer, munasarjasyöpä, Medicine, Prospective Studies, Colectomy, Salpingo-oophorectomy/methods, Database, Manchester Cancer Research Centre, COLON-CANCER, MLH1, WOMEN, Middle Aged, Prognosis, Lynch syndrome, 3. Good health, kohdunrungon syöpä, Oncology, COLECTOMY, 030220 oncology & carcinogenesis, Female, Biomarkers, Tumor/genetics, Adult, Heterozygote, Genital Neoplasms, Female, Salpingo-oophorectomy, Hysterectomy, 03 medical and health sciences, Genital Neoplasms, Female/prevention & control, Ovarian cancer, Colorectal Neoplasms, Hereditary Nonpolyposis/genetics, Biomarkers, Tumor, Mortalitat, Humans, Hysterectomy/methods, Mortality, Lynchin oireyhtymä, Risk-reducing surgery, Aged, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Cancer, MSH6, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, MSH2, 030104 developmental biology, Cross-Sectional Studies, PMS2, Càncer d'endometri, Mutation, kohdunpoisto, business, computer, Follow-Up Studies
Abstract

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.

Published
2021
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36. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Author

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

Subjects
0301 basic medicine, medicine.medical_treatment, DNA Mismatch Repair, Gynecologic surgery, 0302 clinical medicine, Malalties hereditàries, Prospective Studies, Prospective cohort study, Genetics (clinical), Mismatch Repair Endonuclease PMS2, Incidence (epidemiology), Middle Aged, 16. Peace & justice, Lynch syndrome, 3. Good health, 030220 oncology & carcinogenesis, Female, syöpätaudit, MutL Protein Homolog 1, Genetic diseases, Heterozygote, medicine.medical_specialty, Salpingo-oophorectomy, Cirurgia ginecològica, Hysterectomy, Article, 03 medical and health sciences, Càncer colorectal, CAPP2, medicine, Humans, Lynchin oireyhtymä, Gynecology, perinnölliset taudit, HEREDITARY COLORECTAL-CANCER, business.industry, Endometrial cancer, Cancer, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Colorectal cancer, ASPIRIN, 030104 developmental biology, Clinical research, 3121 General medicine, internal medicine and other clinical medicine, kohdunpoisto, 3111 Biomedicine, Ovarian cancer, business
Abstract

Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR ( path_MMR ) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1 , path_MSH2 , path_MSH6 , and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Published
2021
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37. Correction:Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

Author

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

Subjects
Oncology, Male, Colorectal cancer, Lynch syndrome, Penetrance, DNA Mismatch Repair, 0302 clinical medicine, Databases, Genetic, Malalties hereditàries, Prospective Studies, Càncer, PMS2, Genetics (clinical), Mismatch Repair Endonuclease PMS2, Cancer, 0303 health sciences, Sex Characteristics, Factors de risc en les malalties, 1184 Genetics, developmental biology, physiology, MLH1, Middle Aged, 16. Peace & justice, 3. Good health, DNA-Binding Proteins, MutS Homolog 2 Protein, syöpägeenit, MSH2, 030220 oncology & carcinogenesis, MSH6, 030211 gastroenterology & hepatology, DNA mismatch repair, Female, geneettiset tekijät, MutL Protein Homolog 1, Genetic diseases, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Risk factors in diseases, suolistosyövät, MUTATION CARRIERS, Risk Assessment, Article, sukupuoli, Age and gender, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Lynchin oireyhtymä, Gene, 030304 developmental biology, Aged, business.industry, Endometrial cancer, Correction, nutritional and metabolic diseases, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Survival Analysis, digestive system diseases, Mutation, 3111 Biomedicine, ikä, business, Ovarian cancer
Abstract

Lynch syndrome (LS) results from pathogenic variants in the mismatch repair (MMR) genes and is the most common hereditary cancer syndrome, affecting an estimated 1 in 300 individuals. Pathogenic variants in each of the MMR genes path_MLH1, path_MSH2, path_MSH6, and path_PMS2 result in different risks for cancers in organs including the colorectum, endometrium, ovaries, stomach, small bowel, bile duct, pancreas, and upper urinary tract. Accurate estimates of these risks are essential for planning appropriate approaches to the prevention or early diagnosis of cancers but the robustness of previous studies has been limited by factors including retrospective design,1,2 lack of validation in independent cohorts,3-5 and inconsistent classification of genetic variants. Unexpected findings from previous studies have included path_MLH1 and path_MSH2 carriers appearing to have a lifetime risk of colorectal cancer (CRC) of approximately 50%, despite surveillance colonoscopy,6-8 and that shorter intervals between colonoscopies do not seem to reduce the incidence of CRC in LS.9,10 These findings challenge the assumptions that CRC in LS usually develops from a noninfiltrative adenoma precursor and that CRC can be prevented by colonoscopic detection and removal of adenomas in the colon and rectum. Additionally, previous studies in the Prospective Lynch Syndrome Database (PLSD) have shown no increase in cancer risk in path_PMS2 carriers before 40 years of age and, although observation years were limited in older path_PMS2 carriers, LS-associated cancers other than endometrial and prostate were not observed.6-8 In this study we collected prospective data from a new large cohort of path_MMR carriers to validate previous findings from PLSD. We also updated information on the original cohort to ensure consistent classification of pathogenicity of MMR gene variants. We then combined both data sets, providing larger numbers that allowed us to derive more precise risk estimates for cancers in LS categorized by gene and gender.

Published
2020
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38. Feasibility of volatile organic compound in breath analysis in the follow-up of colorectal cancer: A pilot study.

Author

Steenhuis EGM, Schoenaker IJH, de Groot JWB, Fiebrich HB, de Graaf JC, Brohet RM, van Dijk JD, van Westreenen HL, Siersema PD, and de Vos Tot Nederveen Cappel WH

Subjects
Aged, Carcinoma secondary, Case-Control Studies, Colorectal Neoplasms pathology, Feasibility Studies, Female, Humans, Liver Neoplasms secondary, Lung Neoplasms secondary, Machine Learning, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Metastasis, Pilot Projects, Positron-Emission Tomography, ROC Curve, Sensitivity and Specificity, Tomography, X-Ray Computed, Breath Tests methods, Carcinoma diagnosis, Colorectal Neoplasms diagnosis, Electronic Nose, Liver Neoplasms diagnosis, Lung Neoplasms diagnosis, Neoplasm Recurrence, Local diagnosis, Volatile Organic Compounds analysis
Abstract

Background: Colorectal carcinoma (CRC) has a worldwide incidence of 1.4 million patients and a large share in cancer-related mortality. After curative treatment, the risk of recurrence is 30-65%. Early detection may result in curative treatment. However, current follow-up (FU) examinations have low sensitivity ranging from 49 to 85% and are associated with high costs. Therefore, the search for a new diagnostic tool is justified. Analysis of volatile organic compound in exhaled air through an electronic nose (eNose) is a promising new patient-friendly diagnostic tool. We studied whether the eNose under investigation, the Aeonose™, is able to detect local recurrence or metastases of CRC., Methods: In this cross-sectional study we included 62 patients, all of whom underwent curative treatment for CRC in the past 5 years. Thirty-six of them had no metastases and 26 had extraluminal local recurrence or metastases of CRC, detected during FU. Breath testing was performed and machine learning was used to predict extraluminal recurrences or metastases, and based on the receiver operating characteristics (ROC)-curve both sensitivity and specificity were calculated., Results: The eNose identified extra luminal local recurrences or metastases of CRC with a sensitivity and specificity of 0.88 (CI 0.69-0.97) and 0.75 (CI 0.57-0.87), respectively, with an overall accuracy of 0.81., Discussion: This eNose may be a promising tool in detecting extraluminal local recurrences or metastases in the FU of curatively treated CRC. However, a well-designed prospective study is warranted to show its accuracy and predictive value before it can be used in clinical practice., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Published
2020
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40. Consequences of CT colonography in stenosing colorectal cancer.

Author

Huisman JF, Leicher LW, de Boer E, van Westreenen HL, de Groot JW, Holman FA, van de Meeberg PC, Sallevelt P, Peeters K, Wasser M, Vasen H, and de Vos Tot Nederveen Cappel WH

Subjects
Aged, Constriction, Pathologic, Female, Humans, Male, Postoperative Care, Colonoscopy, Colorectal Neoplasms diagnostic imaging, Colorectal Neoplasms pathology, Tomography, X-Ray Computed
Abstract

Background: In patients with stenosing colorectal cancer (CRC), visualization of the entire colon prior to surgery is recommended to exclude synchronous tumors. Therefore, most centers combine computed tomographic colonography (CTC) with staging CT. The aims of this study were to evaluate the yield and clinical implications of CTC., Methods: In this multicenter retrospective study, patients with stenosing CRC that underwent CTC and subsequent surgery between April 2013 and November 2015 were included. Result of the CTC, its influence on the surgical treatment plan, and final histology report were evaluated., Results: One hundred sixty-two patients with stenosing CRC were included. Nine (5.6 %) synchronous cancers proximal to the stenosing tumor were suspected with CTC. In four of nine patients, the CTC did not change the primary surgical plan because the tumors were located in the same surgical segment. In five of nine patients, CTC changed the surgical treatment plan. Three of these five patients underwent an extended resection and the presence of the tumors was confirmed. Two of these three synchronous CRCs were also visible on abdominal staging CT. In the other two patients, the result of CTC was false positive which led to an unnecessary extended resection in one patient., Conclusion: The yield of CTC was relatively low. In only three patients (1.9 %), CTC correctly changed the primary surgical plan, but in two of them, the tumor was also visible on abdominal staging CT. Moreover, in two patients, CTC was false positive. The clinical value of CTC in stenosing CRC appears to be limited.

Published
2017
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42. Double balloon endoscopy for detection of small-bowel adenomas in familial adenomatous polyposis after pancreaticoduodenectomy according to Whipple.

Author

Langers AM, De Vos tot Nederveen Cappel WH, Veenendaal RA, Bonsing BA, Hardwick JC, and Vasen HF

Subjects
Adenoma etiology, Anastomosis, Roux-en-Y, Catheterization, Cholangiopancreatography, Endoscopic Retrograde, Duodenal Diseases surgery, Duodenal Neoplasms etiology, Duodenoscopy, Humans, Intestinal Polyps surgery, Male, Middle Aged, Pancreaticoduodenectomy, Polyps surgery, Recurrence, Adenoma diagnosis, Adenoma surgery, Adenomatous Polyposis Coli complications, Duodenal Neoplasms diagnosis, Duodenal Neoplasms surgery, Endoscopy methods
Abstract

Patients with familial adenomatous polyposis (FAP) have a 5%-10% lifetime risk of developing duodenal cancer. In severe duodenal polyposis, pancreaticoduodenectomy according to Whipple has been considered the only way to cure duodenal polyposis. However, polyps recur even after surgery. We describe a patient with severe adenomatosis of the small bowel in the afferent loop of a Roux-en-Y anastomosis after a Whipple procedure, detected by double balloon endoscopy (DBE). This is the first description of the use of DBE for this indication, and emphasizes the need for surveillance of the small bowel after surgery, especially in the area of the biliary anastomosis.

Published
2008
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43. Liver transplantation in a patient with encapsulating peritoneal sclerosis.

Author

de Vos Tot Nederveen Cappel WH, Dubbeld J, Willems SM, Ringers J, and van Hoek B

Subjects
Aged, Biopsy, Humans, Liver Cirrhosis complications, Liver Cirrhosis pathology, Male, Peritoneal Diseases pathology, Peritoneal Diseases surgery, Sclerosis pathology, Sclerosis surgery, Liver Cirrhosis surgery, Liver Transplantation methods, Peritoneal Diseases complications, Peritoneum pathology
Abstract

Encapsulating peritoneal sclerosis (EPS) is a poorly understood condition in which excess fibrosis results in an encasement of the small bowel, which can clinically result in obstruction. The condition is thought to be related to the persistent expression of transforming growth factor beta on mesothelial cells causing proliferation of subserosal fibroblasts, massive production of extracellular matrix and loss of mesothelial cells. We report a patient with liver cirrhosis in whom the diagnosis of EPS was made. During laparotomy for liver transplantation the complete peritoneum was found to be thickened, consisting of white sheets; liver transplantation was deferred. Histological examination showed peritoneal sclerosing fibrosis. Immunosuppressive medication was started and a difficult but successful liver transplantation followed. If EPS is diagnosed during laparotomy for organ transplantation, adjusted immunosuppression is preferred as calcineurin inhibitors such as cyclosporin and tacrolimus may accelerate EPS while prednisone and some other drugs may stop progression.

Published
2008

44. [Frequency of duodenal adenomas in patients with familial adenomatous polyposis].

Author

van Ruth S, de Vos tot Nederveen Cappel WH, van Laarhoven CJ, and Vasen HF

Subjects
Adenoma diagnosis, Adult, Age Factors, Aged, Duodenal Neoplasms diagnosis, Duodenal Neoplasms secondary, Duodenoscopy, Female, Humans, Incidence, Male, Mass Screening methods, Middle Aged, Netherlands epidemiology, Prevalence, Retrospective Studies, Severity of Illness Index, Adenoma epidemiology, Adenomatous Polyposis Coli complications, Duodenal Neoplasms epidemiology
Abstract

Objective: To estimate the prevalence of polyps in the stomach and duodenum in patients with familial adenomatous polyposis (FAP), and to examine the relationship between age and severity of duodenal adenomatosis., Design: Retrospective., Method: Using the FAP-registry of the Netherlands Foundation for the Detection of Hereditary Tumours, data were obtained from patients who had undergone a gastroduodenoscopy before 1 July 1999. The endoscopic and histological findings were used to classify the duodenal adenomas according to the Spigelman classification., Results: 224 patients had undergone at least one gastroduodenoscopy: 117 men and 107 women with a mean age at the time of the first endoscopy of 37 years (range: 13-78). Fundic gland polyposis was detected in 79 patients (35%), stomach adenomas in 6 patients (3%) and duodenal adenomas in 92 patients (41%). A total of 21 patients (9%) had severe duodenal adenomatosis (Spigelman III or IV). Duodenal adenomatosis was often more severe if the patient was older. Ten patients were known to have duodenal cancer; the mean age at diagnosis was 50.3 years (range: 39-67)., Conclusion: Nearly 10% of the patients with FAP had developed severe duodenal adenomatosis. The severity of duodenal adenomatosis was related to the patient's age.

Published
2001

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