Contenido del artículo principal
Resumen
Introducción: El trasplante renal se ha destacado como la mejor terapia renal sustitutiva para la enfermedad renal crónica terminal, aunque conlleva una serie de riesgos entre los que el cáncer se destaca cada vez más, por lo que parece importante determinar el impacto que tiene en esta población.
Objetivo: Conocer y sintetizar la evidencia científica acerca de la incidencia de neoplasias en pacientes trasplantados renales, así como las variables relacionadas con las mismas.
Metodología: Se realizó una revisión sistemática en la que se incluyeron 14 artículos procedentes de las bases de Pubmed, Scopus, Scielo, WOS y Google Académico. Como términos MeSH se utilizaron: neoplasias (neoplasms), trasplante de riñón (kidney transplantation), incidencia (incidence), riesgo (risk), factores de riesgo (risk factors). Se incluyeron artículos originales en inglés y español, en población trasplantada adulta.
Resultados: Se incluyeron 14 artículos de diseño observacional. De la revisión emergieron como principales variables: incidencia general, datos demográficos y tratamientos previos, otras características asociadas, tumores más frecuentes y medidas preventivas.
Conclusiones: La incidencia de neoplasias en el paciente trasplantado es alta, sobre todo en la edad avanzada y pacientes con tratamiento inmunosupresor con ciclosporina y azatioprina siendo este último, junto al trasplante procedente de cadáver, los principales factores de riesgo encontrados. Los cánceres de piel no melanoma son los más prevalentes y como medidas de prevención se destaca llevar a cabo un cribado rutinario, fomento de una vida saludable, y promoción y potenciación de la vacunación de la hepatitis B.
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Detalles del artículo
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Referencias
- Rodrigo-Orozco B. Prevención y tratamiento de la enfermedad renal crónica (ERC). Rev Med Clín Las Condes 2010; 21(5):779-89. DOI: https://doi.org/10.1016/S0716-8640(10)70600-3
- United Stated Renal Data System: 2017 USRDS annual data report: Epidemiology of kidney disease in the United States [Internet]. Bethesa (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases 2017 [consultado 10 Abr 2022]. Disponible en: https://www.usrds.org/.
- Rama I, Grinyo JM. Malignancy after renal transplantation: the role of immunosuppression. Nat Rev Nephrol 2010; 6(9):511-9. DOI: https://doi.org/10.1038/nrneph.2010.102
- Sprangers B, Nair V, Launay- Vacher V, Riella LV, Jhaveri KD. Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network. Clin Kidney J 2018;11(3):315-29. DOI: https://doi.org/10.1093/ckj/sfx122
- Morath C, Müller M, Goldschmidt H, Schewenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004; 15(6):1582-8. DOI: https://doi.org/10.1097/01.ASN.0000126194.77004.9B
- Cohen-Bucay A, Gordon CE, Francis JM. Non-immunological complications following kidney transplantation . F1000Res. 2019;8:F1000 Faculty Rev-194. DOI: https://doi.org/10.12688/f1000research.16627.1
- Lentine KL, Costa SP, Weir MR, Robb JF, Fleisher LA, Kasiske BL, et al. Cardiac disease evaluation and management among kidney and liver transplantation candidates: a and the American College of Cardiology Foundation. J Am Coll Cardiol 2012;60(5):434-80. DOI: https://doi.org/10.1016/j.jacc.2012.05.008
- Malysko J, Bamias A, Danesh FR, Debska-Slizien A, Gallieni M, Gertz MA, et al. KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantation. Kidney Int 2020;98(6):1407-18. DOI: https://doi.org/10.1016/j.kint.2020.07.012
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- McCaughan JA, Courtney AE. The clinical course of kidney transplant recipients after 20 years of graft function. Am J Transplant 2015;15(3):734-40. DOI: https://doi.org/10.1111/ajt.13041
- Vajdic CM, McDonald SP, McCredie MR, T-Van Leeuwen M, Stewart JH, Law M, et al. Cancer Incidence Before and After Kidney Transplantation. JAMA 2006;296(23):2823-31. DOI: https://doi.org/10.1001/jama.296.23.2823
- Au E, Wong G, Chapman JR. Cancer in kidney transplant recipients. Nat Rev Nephrol 2018;14:508-20. DOI: https://doi.org/10.1038/s41581-018-0022-6
- ANZDATA. ANZDATA 36th Annual Report 2013: Australia and New Zealand Dialysis and Transplant Registry [Internet]. 2014 [consultado 10 Abr 2022]. Disponible en: https://www.anzdata.org.au/report/anzdata-36th-annual-report-2013/.
- Gallagher MP, Kelly PJ, Jardine M, Perkovic V, Cass A, Craig JC, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 2010;21(5):852-8. DOI: https://doi.org/10.1681/ASN.2009101043
- Acuna SA, Huang JW, Scott AL, Micic S, Daly C, Brezden-Masley C, et al. Cancer Screening Recommendations for solid organ transplant recipients: A systematic Review of Clinical Practice Guidelines. Am J Transplant 2017; 17(1):103-14. DOI: https://doi.org/10.1111/ajt.13978
- Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4(6):905-13. DOI: https://doi.org/10.1111/j.1600-6143.2004.00450.x
- Collins L, Asfour L, Stephany M, Lear JT, Stasko T. Management of Non-melanoma Skin Cancer in Transplant Recipients. Clin Oncol (R Coll Radiol) 2019;31(11):779-88. DOI: https://doi.org/10.1016/j.clon.2019.08.005
- Kumar R, Khosla D, Kapoor R, Bharti S. Small intestinal lymphoma in a post-renal transplant patient: a rare case with late presentation. J Gastrointest Cancer 2014;45 (Supl 1):S2-5. DOI: https://doi.org/10.1007/s12029-013-9517-3
- Pérez-Sáez MJ, Canal C, Cofan F, Errasti P, Jimeno L, López-Oliva M, et al. Epidemiología del cáncer en el trasplante renal: incidencia, prevalencia y factores de riesgo. Nefrología Sup Ext [Internet]. 2018 [consultado 10 Abr 2022]; 9(1):24-36. Recuperado a partir de: https://www.revistanefrologia.com/es-epidemiologia-del-cancer-el-trasplante-articulo-X2013757518622259.
- Ma MK, Lim WH, Turner RM, Chapman JR, Craig JC, Wong G. The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis. Transplantation 2014;98(12):1286-93. DOI: https://doi.org/10.1097/TP.0000000000000375
- Wong G, Turner RM, Chapman JR, Howell M, Lim WH, Webster AC, et al. Time on dialysis and cancer risk after kidney transplantation. Transplantation 2013;95(1):114-21. DOI: https://doi.org/10.1097/TP.0b013e31827743b4
- Urrutia G, Bonfill X. Declaración PRISMA: una propuesta para mejorar la publicación de revisiones sistemáticas y metaanálisis. Med Clin 2010;135(11):507-11. DOI: https://doi.org/10.1016/j.medcli.2010.01.015
- Vandenbroucke J, Von E, Altman D, Gøtzsche P, Mulrow C, Pocock S, et al. Mejorar la comunicación de estudios observacionales en epidemiología (STROBE): explicación y elaboración. Gac Sanit 2009;23(2):1-28. DOI: https://doi.org/10.1016/j.gaceta.2008.12.001
- Basic-Jukic N, Kirincich J, Jelakovic B, Kastelan Z. Multiple Primary Malignancies in Renal Transplant Recipients: a Single Centre Retrospective Cohort Study. Kidney Blood Press Res 2018;43:1034-41. DOI: https://doi.org/10.1159/000490825
- Zilinska Z, Sersenova M, Chrastina M, Breza SR J, Bena L, Baltesova T, et al. Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience. Neoplasma 2017;64(2):311-7. DOI: https://doi.org/10.4149/neo_2017_220
- Vieira P, Barreto P, Pedroso S, Almeida M, Martins LS, Días L, et al. Malignancy after renal transplantation: a single-centre experience. Port J Nephrol Hypert [Internet]. 2016 [consultado 11 Abr 2022]; 30(3):205-9. Disponible en: http://hdl.handle.net/10400.16/2243
- Gioco R, Corona D, Agodi A, Privitera F, Barchitta M, Giaquinta A, et al. De Novo Cancer Incidence and Prognosis After Kidney Transplantation: A Single Center Analysis. Transplantation Proceedings 2019;51(9):2927-30. DOI: https://doi.org/10.1016/j.transproceed.2019.04.096
- Abdelfadil Elserwy N, Elden Lotfy E, Ashraf Fouda M, Ibrahim Mahmoud M, Farouk Donia A, Elsayed Mashaly M, et al. Postrenal Transplant Malignancy: Incidence, Risk Factors, and Prognosis. Saudi J Kidney Dis Transpl 2017; 28(3):579-88. DOI: https://doi.org/10.4103/1319-2442.206456
- Fröhlich FA, Halleck F, Lehner L, Schrezenmeier EV, Naik M, Schmidt D, et al. De-novo malignancies after kidney transplantation: A long-term observational study. PLOS ONE 2020;15(11). DOI: https://doi.org/10.1371/journal.pone.0242805
- Heo J, Noh O, Oh YT, Chun M, Kim L. Cancer risk after renal transplantation in South Korea: a nationwide population-based study. BMC Nephrol 2018;19(1):311. DOI: https://doi.org/10.1186/s12882-018-1110-3
- Teo SH, Lee KG, Lim GH, Koo SX, Ramirez ME, Chow KY, et al. Incidence, risk factors and outcomes of malignancies after kidney transplantation in Singapore: a 12-year experience. Singapore Med J 2019;60(5):253-9. DOI: https://doi.org/10.11622/smedj.2018122
- Imamura R, Nakazawa S, Yamanaka K, Kakuta Y, Tsutahara K, Taniguchi A, et al. Cumulative cancer incidence and mortality after kidney transplantation in Japan: A long-term multicenter cohort study. Cancer Med 2020; 10(7):2205-15. DOI: https://doi.org/10.1002/cam4.3636
- Jeong S, Lee HS, Kong SG, Kim DJ, Lee S, Park MJ, et al. Incidence of malignancy and related mortality after kidney transplantation: a nationwide, population-based cohort study in Korea. Sci Rep 2020;10(21398). DOI: https://doi.org/10.1038/s41598-020-78283-5
- Nejatifar F, Monfared A, Khosravi M, Lebadi M, Shakiba M, Mokhtari G, et al. Incidence and Risk Factors of Post-renal Transplantation Malignancies in North of Iran, A 20-year Experience. Iran J Kidney Dis. [Internet]. 2020 [consultado 14 Abr 2022]; 14(6):439-47. Disponible en: http://www.ijkd.org/index.php/ijkd/article/view/5861/1214
- Benoni H, Eloranta S, Dahle DO, Svensson MHS, Nordin A, Carstens J, et al. Relative and absolute cancer risks among Nordic kidney transplant recipients- a population-based study. Transpl Int 2020;33(12):1700-10. DOI: https://doi.org/10.1111/tri.13734
- Schrem H, Schneider V, Kurok M, Goldis A, Dreier M, Kaltenborn A, et al. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control. PLOS ONE 2016;11(7). DOI: https://doi.org/10.1371/journal.pone.0158732
- Helmy S, Marschalek J, Bader Y, Koch M, Schmidt A, Kanzler M, et al. Risk Factors for De Novo Malignancies in Women After Kidney Transplantation: A Multicenter Transversal Study. International Journal of Gynecological Cancer 2016;26(5):967-70. DOI: https://doi.org/10.1097/IGC.0000000000000710
- Lee KF, Tsai YT, Lin CY, Hsieh CB, Wu ST, Ke HY, et al. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan. PLOS ONE 2016;11(5). DOI: https://doi.org/10.1371/journal.pone.0155602
- Yeh CC, Khan A, Muo CH, Yang HR, Li PC, Chang CH, et al. De Novo Malignancy After Heart, Kidney, and Liver Transplant: A Nationwide Study in Taiwan. Exp Clin Transplant 2020;18(2):224-33. DOI: https://doi.org/10.6002/ect.2019.0210
- Park B, Yoon J, Choi D, Kim HJ, Jung YK, Kwon OJ, et al. De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data. Sci Rep 2019;9(17202). DOI: https://doi.org/10.1038/s41598-019-53163-9
- Mazzucotelli V, Piselli P, Verdirosi D, Cimaglia C, Cancarini G, Serraino D, et al. De novo cancer in patients on dialysis and after renal transplantation: north-western Italy, 1997-2012. J Nephrol 2017;30(6):851-7. DOI: https://doi.org/10.1007/s40620-017-0385-y
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Referencias
Rodrigo-Orozco B. Prevención y tratamiento de la enfermedad renal crónica (ERC). Rev Med Clín Las Condes 2010; 21(5):779-89. DOI: https://doi.org/10.1016/S0716-8640(10)70600-3
United Stated Renal Data System: 2017 USRDS annual data report: Epidemiology of kidney disease in the United States [Internet]. Bethesa (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases 2017 [consultado 10 Abr 2022]. Disponible en: https://www.usrds.org/.
Rama I, Grinyo JM. Malignancy after renal transplantation: the role of immunosuppression. Nat Rev Nephrol 2010; 6(9):511-9. DOI: https://doi.org/10.1038/nrneph.2010.102
Sprangers B, Nair V, Launay- Vacher V, Riella LV, Jhaveri KD. Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network. Clin Kidney J 2018;11(3):315-29. DOI: https://doi.org/10.1093/ckj/sfx122
Morath C, Müller M, Goldschmidt H, Schewenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004; 15(6):1582-8. DOI: https://doi.org/10.1097/01.ASN.0000126194.77004.9B
Cohen-Bucay A, Gordon CE, Francis JM. Non-immunological complications following kidney transplantation . F1000Res. 2019;8:F1000 Faculty Rev-194. DOI: https://doi.org/10.12688/f1000research.16627.1
Lentine KL, Costa SP, Weir MR, Robb JF, Fleisher LA, Kasiske BL, et al. Cardiac disease evaluation and management among kidney and liver transplantation candidates: a and the American College of Cardiology Foundation. J Am Coll Cardiol 2012;60(5):434-80. DOI: https://doi.org/10.1016/j.jacc.2012.05.008
Malysko J, Bamias A, Danesh FR, Debska-Slizien A, Gallieni M, Gertz MA, et al. KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantation. Kidney Int 2020;98(6):1407-18. DOI: https://doi.org/10.1016/j.kint.2020.07.012
ANZDATA. ANZDATA: 41st Annual ANZDATA Report [Internet]. 2018 [consultado 10 de abril de 2022]. Disponible en: https://www.anzdata.org.au/report/anzdata-41st-annual-report-2018-anzdata/#:~:text=The%2041st%20Annual%20ANZDATA%20Report,within%20Australia%20and%20New%20Zealand.
McCaughan JA, Courtney AE. The clinical course of kidney transplant recipients after 20 years of graft function. Am J Transplant 2015;15(3):734-40. DOI: https://doi.org/10.1111/ajt.13041
Vajdic CM, McDonald SP, McCredie MR, T-Van Leeuwen M, Stewart JH, Law M, et al. Cancer Incidence Before and After Kidney Transplantation. JAMA 2006;296(23):2823-31. DOI: https://doi.org/10.1001/jama.296.23.2823
Au E, Wong G, Chapman JR. Cancer in kidney transplant recipients. Nat Rev Nephrol 2018;14:508-20. DOI: https://doi.org/10.1038/s41581-018-0022-6
ANZDATA. ANZDATA 36th Annual Report 2013: Australia and New Zealand Dialysis and Transplant Registry [Internet]. 2014 [consultado 10 Abr 2022]. Disponible en: https://www.anzdata.org.au/report/anzdata-36th-annual-report-2013/.
Gallagher MP, Kelly PJ, Jardine M, Perkovic V, Cass A, Craig JC, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 2010;21(5):852-8. DOI: https://doi.org/10.1681/ASN.2009101043
Acuna SA, Huang JW, Scott AL, Micic S, Daly C, Brezden-Masley C, et al. Cancer Screening Recommendations for solid organ transplant recipients: A systematic Review of Clinical Practice Guidelines. Am J Transplant 2017; 17(1):103-14. DOI: https://doi.org/10.1111/ajt.13978
Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4(6):905-13. DOI: https://doi.org/10.1111/j.1600-6143.2004.00450.x
Collins L, Asfour L, Stephany M, Lear JT, Stasko T. Management of Non-melanoma Skin Cancer in Transplant Recipients. Clin Oncol (R Coll Radiol) 2019;31(11):779-88. DOI: https://doi.org/10.1016/j.clon.2019.08.005
Kumar R, Khosla D, Kapoor R, Bharti S. Small intestinal lymphoma in a post-renal transplant patient: a rare case with late presentation. J Gastrointest Cancer 2014;45 (Supl 1):S2-5. DOI: https://doi.org/10.1007/s12029-013-9517-3
Pérez-Sáez MJ, Canal C, Cofan F, Errasti P, Jimeno L, López-Oliva M, et al. Epidemiología del cáncer en el trasplante renal: incidencia, prevalencia y factores de riesgo. Nefrología Sup Ext [Internet]. 2018 [consultado 10 Abr 2022]; 9(1):24-36. Recuperado a partir de: https://www.revistanefrologia.com/es-epidemiologia-del-cancer-el-trasplante-articulo-X2013757518622259.
Ma MK, Lim WH, Turner RM, Chapman JR, Craig JC, Wong G. The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis. Transplantation 2014;98(12):1286-93. DOI: https://doi.org/10.1097/TP.0000000000000375
Wong G, Turner RM, Chapman JR, Howell M, Lim WH, Webster AC, et al. Time on dialysis and cancer risk after kidney transplantation. Transplantation 2013;95(1):114-21. DOI: https://doi.org/10.1097/TP.0b013e31827743b4
Urrutia G, Bonfill X. Declaración PRISMA: una propuesta para mejorar la publicación de revisiones sistemáticas y metaanálisis. Med Clin 2010;135(11):507-11. DOI: https://doi.org/10.1016/j.medcli.2010.01.015
Vandenbroucke J, Von E, Altman D, Gøtzsche P, Mulrow C, Pocock S, et al. Mejorar la comunicación de estudios observacionales en epidemiología (STROBE): explicación y elaboración. Gac Sanit 2009;23(2):1-28. DOI: https://doi.org/10.1016/j.gaceta.2008.12.001
Basic-Jukic N, Kirincich J, Jelakovic B, Kastelan Z. Multiple Primary Malignancies in Renal Transplant Recipients: a Single Centre Retrospective Cohort Study. Kidney Blood Press Res 2018;43:1034-41. DOI: https://doi.org/10.1159/000490825
Zilinska Z, Sersenova M, Chrastina M, Breza SR J, Bena L, Baltesova T, et al. Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience. Neoplasma 2017;64(2):311-7. DOI: https://doi.org/10.4149/neo_2017_220
Vieira P, Barreto P, Pedroso S, Almeida M, Martins LS, Días L, et al. Malignancy after renal transplantation: a single-centre experience. Port J Nephrol Hypert [Internet]. 2016 [consultado 11 Abr 2022]; 30(3):205-9. Disponible en: http://hdl.handle.net/10400.16/2243
Gioco R, Corona D, Agodi A, Privitera F, Barchitta M, Giaquinta A, et al. De Novo Cancer Incidence and Prognosis After Kidney Transplantation: A Single Center Analysis. Transplantation Proceedings 2019;51(9):2927-30. DOI: https://doi.org/10.1016/j.transproceed.2019.04.096
Abdelfadil Elserwy N, Elden Lotfy E, Ashraf Fouda M, Ibrahim Mahmoud M, Farouk Donia A, Elsayed Mashaly M, et al. Postrenal Transplant Malignancy: Incidence, Risk Factors, and Prognosis. Saudi J Kidney Dis Transpl 2017; 28(3):579-88. DOI: https://doi.org/10.4103/1319-2442.206456
Fröhlich FA, Halleck F, Lehner L, Schrezenmeier EV, Naik M, Schmidt D, et al. De-novo malignancies after kidney transplantation: A long-term observational study. PLOS ONE 2020;15(11). DOI: https://doi.org/10.1371/journal.pone.0242805
Heo J, Noh O, Oh YT, Chun M, Kim L. Cancer risk after renal transplantation in South Korea: a nationwide population-based study. BMC Nephrol 2018;19(1):311. DOI: https://doi.org/10.1186/s12882-018-1110-3
Teo SH, Lee KG, Lim GH, Koo SX, Ramirez ME, Chow KY, et al. Incidence, risk factors and outcomes of malignancies after kidney transplantation in Singapore: a 12-year experience. Singapore Med J 2019;60(5):253-9. DOI: https://doi.org/10.11622/smedj.2018122
Imamura R, Nakazawa S, Yamanaka K, Kakuta Y, Tsutahara K, Taniguchi A, et al. Cumulative cancer incidence and mortality after kidney transplantation in Japan: A long-term multicenter cohort study. Cancer Med 2020; 10(7):2205-15. DOI: https://doi.org/10.1002/cam4.3636
Jeong S, Lee HS, Kong SG, Kim DJ, Lee S, Park MJ, et al. Incidence of malignancy and related mortality after kidney transplantation: a nationwide, population-based cohort study in Korea. Sci Rep 2020;10(21398). DOI: https://doi.org/10.1038/s41598-020-78283-5
Nejatifar F, Monfared A, Khosravi M, Lebadi M, Shakiba M, Mokhtari G, et al. Incidence and Risk Factors of Post-renal Transplantation Malignancies in North of Iran, A 20-year Experience. Iran J Kidney Dis. [Internet]. 2020 [consultado 14 Abr 2022]; 14(6):439-47. Disponible en: http://www.ijkd.org/index.php/ijkd/article/view/5861/1214
Benoni H, Eloranta S, Dahle DO, Svensson MHS, Nordin A, Carstens J, et al. Relative and absolute cancer risks among Nordic kidney transplant recipients- a population-based study. Transpl Int 2020;33(12):1700-10. DOI: https://doi.org/10.1111/tri.13734
Schrem H, Schneider V, Kurok M, Goldis A, Dreier M, Kaltenborn A, et al. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control. PLOS ONE 2016;11(7). DOI: https://doi.org/10.1371/journal.pone.0158732
Helmy S, Marschalek J, Bader Y, Koch M, Schmidt A, Kanzler M, et al. Risk Factors for De Novo Malignancies in Women After Kidney Transplantation: A Multicenter Transversal Study. International Journal of Gynecological Cancer 2016;26(5):967-70. DOI: https://doi.org/10.1097/IGC.0000000000000710
Lee KF, Tsai YT, Lin CY, Hsieh CB, Wu ST, Ke HY, et al. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan. PLOS ONE 2016;11(5). DOI: https://doi.org/10.1371/journal.pone.0155602
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Park B, Yoon J, Choi D, Kim HJ, Jung YK, Kwon OJ, et al. De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data. Sci Rep 2019;9(17202). DOI: https://doi.org/10.1038/s41598-019-53163-9
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