1
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Okumi M, Inoue Y, Miyashita M, Ueda T, Fujihara A, Hongo F, Ukimua O. Genitourinary malignancies in kidney transplant recipients. Int J Urol 2024; 31:1321-1329. [PMID: 39316503 DOI: 10.1111/iju.15588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/09/2024] [Indexed: 09/26/2024]
Abstract
Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.
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Affiliation(s)
- Masayoshi Okumi
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuta Inoue
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masatsugu Miyashita
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takashi Ueda
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsuko Fujihara
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Fumiya Hongo
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Osamu Ukimua
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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2
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Sesa V, Silovski H, Basic-Jukic N, Kosuta I, Sremac M, Mrzljak A. Genitourinary tumors and liver transplantation: A comprehensive review. World J Transplant 2024; 14:95987. [PMID: 39295969 PMCID: PMC11317849 DOI: 10.5500/wjt.v14.i3.95987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/28/2024] [Accepted: 06/18/2024] [Indexed: 07/31/2024] Open
Abstract
Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease, but the persistent organ shortage emphasizes a need to explore unconventional donor sources, including individuals with a history of malignancies. This review investigates the viability of liver donation from individuals with current or past genitourinary malignancies, focusing on renal, prostate and urinary bladder cancers. The rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor age. Analysis of transmission risks reveals low rates of donor-derived cancer transmission, particularly for early-stage renal and prostate cancers. Recipients with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer recurrence. Nonetheless, the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management strategies. Recommendations for pre-transplant evaluation and post-transplant surveillance are discussed, highlighting the need for individualized approaches in this patient population. Further prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.
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Affiliation(s)
- Vibor Sesa
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Hrvoje Silovski
- Department of Hepatobiliary Surgery and Transplantation, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Nikolina Basic-Jukic
- Department of Medicine, School of Medicine, Zagreb 10000, Croatia
- Department of Nephrology, Arterial hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Maja Sremac
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
- Department of Medicine, School of Medicine, Zagreb 10000, Croatia
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3
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Fanizza J, Bencardino S, Allocca M, Furfaro F, Zilli A, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S, D'Amico F. Inflammatory Bowel Disease and Colorectal Cancer. Cancers (Basel) 2024; 16:2943. [PMID: 39272800 PMCID: PMC11394070 DOI: 10.3390/cancers16172943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.
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Affiliation(s)
- Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privè Ambroise Parè-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
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4
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Watt KD, Rolak S, Foley DP, Plichta JK, Pruthi S, Farr D, Zwald FO, Carvajal RD, Dudek AZ, Sanger CB, Rocco R, Chang GJ, Dizon DS, Langstraat CL, Teoh D, Agarwal PK, Al-Qaoud T, Eggener S, Kennedy CC, D'Cunha J, Mohindra NA, Stewart S, Habermann TH, Schuster S, Lunning M, Shah NN, Gertz MA, Mehta J, Suvannasankha A, Verna E, Farr M, Blosser CD, Hammel L, Al-Adra DP. Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion. Transplantation 2024:00007890-990000000-00757. [PMID: 38771067 DOI: 10.1097/tp.0000000000005056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.
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Affiliation(s)
| | - Stacey Rolak
- Department of Medicine, Mayo Clinic, Rochester, MN
| | - David P Foley
- Department of Surgery, University of Wisconsin, Madison, WI
| | | | | | - Deborah Farr
- Department of Surgery, University of Texas Southwestern, Dallas, TX
| | - Fiona O Zwald
- Department of Dermatology, Colorado University School of Medicine, Aurora, CO
| | - Richard D Carvajal
- Department of Medicine, Northwell Health Cancer Institute, Lake Success, NY
| | | | - Cristina B Sanger
- Department of Surgery, University of Wisconsin, Madison, WI
- Department of Surgery, William S.Middleton Memorial Veteran's Hospital, Madison, WI
| | - Ricciardi Rocco
- Department of Surgery, Massachusetts General Hospital, Boston MA
| | - George J Chang
- Department of Colon and Rectal Surgery, University of Texas, MD Anderson Cancer Center, Dallas, TX
| | - Don S Dizon
- Department of Medicine, Lifespan Cancer Institute and Brown University, Providence, RI
| | | | - Deanna Teoh
- Department of Obstetrics and Gynecology and Women's Health, University of Minnesota, Minneapolis, MN
| | - Piyush K Agarwal
- Department of Surgery, Section of Urology, University of Chicago, Chicago, IL
| | - Talal Al-Qaoud
- Department of Surgery, Medstar Georgetown Transplant Institute, Georgetown University Hospital, Washington DC
| | - Scott Eggener
- Department of Surgery, Section of Urology, University of Chicago, Chicago, IL
| | | | | | - Nisha A Mohindra
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Shelby Stewart
- Department of Thoracic Surgery, University of Maryland, Baltimore, MD
| | | | - Stephen Schuster
- Department of Medicine, Lymphoma Program, Abraham Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Matthew Lunning
- Department of Medicine, University of Nebraska Medical Center, Omaha, NE
| | - Nirav N Shah
- Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
| | | | - Jayesh Mehta
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Attaya Suvannasankha
- Department of Medicine, Indiana University School of Medicine and Roudebush VAMC, Indianapolis, IN
| | | | - Maryjane Farr
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Christopher D Blosser
- Department of Medicine, University of Washington and Seattle Children's Hospital, Seattle WA
| | - Laura Hammel
- Department of Anesthesiology, University of Wisconsin, Madison, WI
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5
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Steinberg RS, Nayak A, Okoh A, Wang J, Matiello E, Morris AA, Cowger JA, Nohria A. Associations Between Preimplant Cancer Type and Left Ventricular Assist Device Outcomes: An INTERMACS Registry Analysis. ASAIO J 2024; 70:272-279. [PMID: 38039542 DOI: 10.1097/mat.0000000000002108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2023] Open
Abstract
We used the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to examine whether history of a solid versus hematologic malignancy impacts outcomes after left ventricular assist device (LVAD) implantation. We included LVAD recipients (2007-2017) with cancer history reported (N = 14,799, 21% female, 24% Black). Multivariate models examined the association between cancer type and post-LVAD mortality and adverse events. Competing risk analyses compared death and heart transplantation between cancer types and those without cancer in bridge-to-transplant (BTT) patients. A total of 909 (6.1%) patients had a history of cancer (4.9% solid tumor, 1.3% hematologic malignancy). Solid tumors were associated with higher mortality (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.09-1.57), major bleeding (aHR = 1.15, 95% CI = 1.00-1.32), and pump thrombosis (aHR = 1.52, 95% CI = 1.09-2.13), whereas hematologic malignancies were associated with increased major infection (aHR = 1.43, 95% CI = 1.14-1.80). Compared to BTT patients without a history of cancer, solid tumor patients were less likely to undergo transplantation (adjusted subdistribution HR [aSHR] = 0.63, 95% CI = 0.45-0.89) and hematologic malignancy patients were as likely to experience death (aSHR = 1.16, 95% CI = 0.63-2.14) and transplantation (aSHR = 0.69, 95% CI = 0.44-1.08). Cancer history and type impact post-LVAD outcomes. As LVAD utilization in cancer survivors increases, we need strategies to improve post-LVAD outcomes in these patients.
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Affiliation(s)
- Rebecca S Steinberg
- From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Aditi Nayak
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alexis Okoh
- From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Jeffrey Wang
- From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Erin Matiello
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alanna A Morris
- From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Jennifer A Cowger
- Division of Cardiology, Department of Medicine, Henry Ford Health, Detroit, Michigan
| | - Anju Nohria
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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6
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Chukwu CA, Wu HH, Pullerits K, Garland S, Middleton R, Chinnadurai R, Kalra PA. Incidence, Risk Factors, and Outcomes of De Novo Malignancy following Kidney Transplantation. J Clin Med 2024; 13:1872. [PMID: 38610636 PMCID: PMC11012944 DOI: 10.3390/jcm13071872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 03/17/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.
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Affiliation(s)
- Chukwuma A. Chukwu
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK; (C.A.C.); (R.M.); (P.A.K.)
| | - Henry H.L. Wu
- Renal Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, NSW 2065, Australia;
| | - Kairi Pullerits
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK; (K.P.); (S.G.)
| | - Shona Garland
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK; (K.P.); (S.G.)
| | - Rachel Middleton
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK; (C.A.C.); (R.M.); (P.A.K.)
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK; (C.A.C.); (R.M.); (P.A.K.)
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK; (K.P.); (S.G.)
| | - Philip A. Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK; (C.A.C.); (R.M.); (P.A.K.)
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK; (K.P.); (S.G.)
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Yoon J, Kim H, Choi D, Park B. Causes of death and associated factors with death after liver transplantation: a nationwide database study. HPB (Oxford) 2024; 26:54-62. [PMID: 37775353 DOI: 10.1016/j.hpb.2023.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/07/2023] [Accepted: 09/11/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND/AIMS This study investigated overall, 1-year, and 5-year mortality rate, the causes of death, and associated factors with death in liver transplantation recipients. METHODS A total of 11,590 liver transplant recipients identified from National Health Insurance Service database between 2006 and 2017 were included. Factors associated with all-cause of death were analyzed by Cox proportional regression models. Cumulative mortality rate according to the underlying indication was estimated by Kaplan-Meier method. RESULTS The 12-year survival rate for all liver transplant recipients was 68%. In the overall, 1-year, and 5-year mortality of liver transplant recipients, hepatic death was the highest contributing risk, accounting for >65% of the causes of death. Deaths from cirrhosis and liver failure accounted for a high proportion of deaths within 1 year after transplantation, and deaths from malignant tumors such as hepatocellular carcinoma were high among late-stage deaths. DISCUSSION Although the most common cause of death from liver transplantation is due to primary disease, there was a difference in the pattern of major causes of death according to the period from transplantation to death. If appropriate medical intervention is performed at each period after transplantation, the survival rate can be improved.
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Affiliation(s)
- Junghyun Yoon
- Department of Preventive Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
| | - Hanjoon Kim
- Department of Surgery, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
| | - Boyoung Park
- Department of Preventive Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
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8
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Massicotte-Azarniouch D, Noel JA, Knoll GA. Epidemiology of Cancer in Kidney Transplant Recipients. Semin Nephrol 2024; 44:151494. [PMID: 38538455 DOI: 10.1016/j.semnephrol.2024.151494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2024]
Abstract
Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.
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Affiliation(s)
- David Massicotte-Azarniouch
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
| | - J Ariana Noel
- Department of Medicine, University of Ottawa, Ottawa, Canada
| | - Greg A Knoll
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
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9
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Schroder PM, Biesterveld BE, Al-Adra DP. Premalignant Lesions in the Kidney Transplant Candidate. Semin Nephrol 2024; 44:151495. [PMID: 38490902 DOI: 10.1016/j.semnephrol.2024.151495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population. High-level evidence for the management of these rarer premalignant lesions in the transplant population is lacking, and this review extrapolates evidence from the general population and should not be a substitute for a multidisciplinary discussion with medical and surgical oncologists.
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Affiliation(s)
- Paul M Schroder
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Ben E Biesterveld
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - David P Al-Adra
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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10
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Wong G, Lim WH. Prior cancer history and suitability for kidney transplantation. Clin Kidney J 2023; 16:1908-1916. [PMID: 37915927 PMCID: PMC10616492 DOI: 10.1093/ckj/sfad141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Indexed: 11/03/2023] Open
Abstract
Kidney transplantation is the optimal treatment for most patients with kidney failure. For patients with a prior history of treated cancers, listing and transplant eligibility decisions are complex. Patients and health professionals are obliged to consider the time-periods between cancer cure and transplantation, the risk of cancer recurrence under the influence of immunosuppression and anti-cancer treatment options if the disease recurs. Cancer recurrence is associated with a high mortality rate, thus potentially reduces the projected survival benefit of transplantation, and dampens the utility of scarce organs. In view of the uncertain risk of harms, clinicians may consider transplantation for candidates with prior cancer history only after an extended period of cancer-free interval, as the fear of disease recurrence and shortened life expectancy may outweigh the benefits of receiving a kidney transplant compared with dialysis. Over the past decade, the evolution of novel anti-cancer therapies coupled with improved understanding of cancer genomics have led to considerable improvement in cancer-free survival. It is therefore justifiable to make individualized transplant suitability decisions based the joint effects of cancer biology, available therapeutic options and prognostic covariates on clinical outcomes. In this review, we first summarized the cancer epidemiology in kidney transplant recipients. We then explored how the probability of cancer cure, risk of recurrence and outcomes in candidates with a prior cancer history may influence the decisions to transplant. Finally, the role of shared decision-making between health professionals and patients regarding the optimal management options, and considerations of patients' preferences and values are discussed.
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Affiliation(s)
- Germaine Wong
- Sydney School of Public Health, University of Sydney, Camperdown, NSW, Australia
- Centre for Kidney Research, Kids Research Institute, The Children's Hospital at Westmead, NSW, Sydney, Australia
- Centre for Kidney and Transplantation Research, Westmead Hospital, NSW, Sydney, Australia
| | - Wai H Lim
- Department of Renal and Transplantation Medicine, Sir Charles Gairdner Hospital, WA, Perth, Australia
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11
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Borin A, Caldonazzi N, Eccher A, Bortolasi L, Bosio C, Bronzoni C, Violi P, Pastorelli D, Rizzo PC, Carraro A. ABO-Incompatible Orthotopic Liver Transplant as a Rescue Strategy for Fulminant Hepatic Failure in a Recipient With Breast Cancer: Highlights on Transplant Management. EXP CLIN TRANSPLANT 2023; 21:779-783. [PMID: 37885295 DOI: 10.6002/ect.2023.0238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
Pretransplant malignancy unrelated to hepatocellular carcinoma is a challenging condition in liver transplantation. Standard of care requires the completion of treatments and a disease-free period before the transplant. However, in the setting of a fulminant hepatic failure, these steps cannot be achieved. A 46-year-old woman with a recent diagnosis of stage 2 breast cancer presented to our center with a fulminant hepatic failure of unknown origin. Because of the rapid worsening of her clinical status, she was listed as eligible for transplant after a multidisciplinary evaluation. Because of a shortage of available donors, a deceased donor ABO-incompatible liver transplant with a synchronous mastectomy and first-level axillary lymphadenectomy was performed. To prevent antibody-mediated rejection, a triple immunosuppression therapy and a postoperative therapeutic plasmapheresis were performed. The patient remains without cancer recurrence at 18 months of follow-up. Recent studies have shown that cancer recurrence in recipients with pretransplant malignancy is considerably lower than suggested in previously published studies. However,this data is not sufficient to establish evidence-based guidelines on the indications and timing of transplant. In selected cases, the presence of a pretransplant malignancy does notrepresent a contraindication for a rescue liver transplant. Further studies are needed to stratify the risk and to help clinicians to choose the best strategy in an urgent context such as this.
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Affiliation(s)
- Alex Borin
- From the Department of General Surgery and Dentistry, Liver Transplant Unit, University and Hospital Trust of Verona, Verona, Italy
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12
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Yang Z, Xie H, Wan J, Wang Y, Zhang L, Zhou K, Tang H, Zhao W, Wang H, Song P, Zheng S. A nanotherapeutic strategy that engages cytotoxic and immunosuppressive activities for the treatment of cancer recurrence following organ transplantation. EBioMedicine 2023; 92:104594. [PMID: 37167784 DOI: 10.1016/j.ebiom.2023.104594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 04/16/2023] [Accepted: 04/17/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Long-term treatment with immunosuppressants is necessary to attenuate allograft rejection following organ transplantation (OT). Consequently, the overall survival of OT recipients with malignancies has been substantially compromised by tumour recurrence. Rapamycin (RAPA) is a clinically approved immunosuppressive agent with antitumour activity that is considered beneficial in preventing posttransplant tumour recurrence. However, the clinical outcome of RAPA is impeded by acquired drug resistance and its poor oral bioavailability. METHODS A nanotherapeutic strategy was developed by supramolecular assembly of RAPA into a polymer cytotoxic 7-ethyl-10-hydroxycamptothecin (SN38) prodrug nanoparticle (termed SRNP) for simultaneous codelivery of cytotoxic/immunosuppressive agents. Cell-based experiments were used to evaluate the cytotoxicity of SRNPs against hepatocellular carcinoma (HCC). The therapeutic efficacy of SRNPs was evaluated in multiple preclinical models including an orthotopic HCC mouse model, an orthotopic liver transplantation (OLT) rat model and a clinically relevant cancer-transplant model to examine its antitumour and immunosuppressive activity. FINDINGS The combination of SN38 with RAPA resulted in synergetic effects against HCC cells and alleviated RAPA resistance by abrogating Akt/mTOR signalling activation. SRNPs exhibited potent antitumour efficiency in the orthotopic HCC model while substantially prolonging the survival of allografts in the OLT model. In the cancer-transplant model that simultaneously bears tumour xenografts and skin allografts, SRNPs not only effectively inhibited tumour growth but also attenuated allograft damage. INTERPRETATION The nanotherapy presented here had enhanced efficacy against tumours and maintained satisfactory immunosuppressive activity and thus has great potential to improve the survival outcomes of patients with a high risk of tumour recurrence following OT. FUNDING This work was supported by the National Natural Science Foundation of China (32171368 and 31671019), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Zhejiang Province Preeminence Youth Fund (LR19H160002), and the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c).
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Affiliation(s)
- Zhentao Yang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China.
| | - Jianqin Wan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yuchen Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Liang Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ke Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hong Tang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Wentao Zhao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hangxiang Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Penghong Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China.
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China.
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13
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Wetwittayakhlang P, Tselekouni P, Al-Jabri R, Bessissow T, Lakatos PL. The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer. J Clin Med 2023; 12:jcm12062432. [PMID: 36983432 PMCID: PMC10056442 DOI: 10.3390/jcm12062432] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand
| | - Paraskevi Tselekouni
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Reem Al-Jabri
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary
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14
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Rudym D, Natalini JG, Trindade AJ. Listing Dilemmas: Age, Frailty, Weight, Preexisting Cancers, and Systemic Diseases. Clin Chest Med 2023; 44:35-46. [PMID: 36774166 DOI: 10.1016/j.ccm.2022.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Selection of lung transplant candidates is an evolving field that pushes the boundaries of what is considered the norm. Given the continually changing demographics of the typical lung transplant recipient as well as the growing list of risk factors that predispose patients to poor posttransplant outcomes, we explore the dilemmas in lung transplant candidate selections pertaining to older age, frailty, low and high body mass index, preexisting cancers, and systemic autoimmune rheumatic diseases.
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Affiliation(s)
- Darya Rudym
- Division of Pulmonary and Critical Care Medicine, New York University, Langone Health, 530 First Avenue, HCC-4A, New York, NY 10016, USA.
| | - Jake G Natalini
- Division of Pulmonary and Critical Care Medicine, New York University, Langone Health, 530 First Avenue, HCC-4A, New York, NY 10016, USA
| | - Anil J Trindade
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Oxford House, Room 539, 1313 21st Avenue South, Nashville, TN 37232, USA
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15
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Hart A, Pfeiffer RM, Morawski BM, Lynch CF, Zeng Y, Pawlish K, Hurley D, Yu KJ, Engels EA. Mortality among solid organ transplant recipients with a pretransplant cancer diagnosis. Am J Transplant 2023; 23:257-264. [PMID: 36804133 PMCID: PMC9978936 DOI: 10.1016/j.ajt.2022.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 10/10/2022] [Accepted: 11/08/2022] [Indexed: 01/15/2023]
Abstract
Little is known about the outcomes among solid organ transplant recipients with a pretransplant cancer diagnosis. We used linked data from the Scientific Registry of Transplant Recipients with 33 US cancer registries. Cox proportional hazards models assessed associations of pretransplant cancer with overall mortality, cancer-specific mortality, and development of a new posttransplant cancer. Among 311 677 recipients, the presence of a single pretransplant cancer was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.23) and cancer-specific mortality (aHR, 1.93; 95% CI, 1.76-2.12); results for 2+ pretransplant cancers were similar. Cancer-specific mortality was not significantly increased for uterine, prostate, or thyroid cancers (aHRs were 0.83, 1.22, and 1.54, respectively) but strongly elevated for lung cancer and myeloma (aHRs were 3.72 and 4.42, respectively). A pretransplant cancer diagnosis was also associated with increased risk of developing posttransplant cancer (aHR, 1.32; 95% CI, 1.23-1.40). Among 306 recipients whose cancer death was confirmed by cancer registry data, 158 deaths (51.6%) were from a de novo posttransplant cancer and 105 (34.3%) from the pretransplant cancer. Pretransplant cancer diagnoses are associated with increased mortality after transplantation, but some deaths are related to posttransplant cancers and other causes. Improved candidate selection and cancer screening and prevention may reduce mortality in this population.
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Affiliation(s)
- Allyson Hart
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA.
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Bozena M Morawski
- Cancer Data Registry of Idaho, Idaho Hospital Association, Boise, Idaho, USA
| | - Charles F Lynch
- University of Iowa Department of Epidemiology, Iowa City, Iowa, USA
| | - Yun Zeng
- University of North Dakota Department of Pathology, North Dakota Statewide Cancer Registry, Grand Forks, North Dakota, USA
| | - Karen Pawlish
- New Jersey State Cancer Registry, New Jersey Department of Health, Trenton, New Jersey, USA
| | - Deborah Hurley
- South Carolina Central Cancer Registry Bureau of Chronic Disease & Injury Prevention, Columbia, South Carolina, USA
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
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16
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Serkies K, Dębska-Ślisień A, Kowalczyk A, Lizakowski S, Małyszko J. Malignancies in adult kidney transplant candidates and recipients: current status. Nephrol Dial Transplant 2022:6674222. [PMID: 35998321 DOI: 10.1093/ndt/gfac239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation including KTRs relative to the general population, most pronounced for skin cancers associated with UV radiation and virally-mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy of cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in the management. Reduction of immunosuppression and the use of mTOR inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Diseases Improving Global Outcome (KDIGO) and American Society of Transplantation (AST) for transplant candidates with a history of cancer are presented.
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Affiliation(s)
- Krystyna Serkies
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland
| | - Alicja Dębska-Ślisień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland
| | - Anna Kowalczyk
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland
| | - Sławomir Lizakowski
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis and Internal Medicine, Warsaw Medical University, Poland
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17
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Piana A, Andras I, Diana P, Verri P, Gallioli A, Campi R, Prudhomme T, Hevia V, Boissier R, Breda A, Territo A. Small renal masses in kidney transplantation: overview of clinical impact and management in donors and recipients. Asian J Urol 2022; 9:208-214. [PMID: 36035353 PMCID: PMC9399547 DOI: 10.1016/j.ajur.2022.06.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 03/24/2022] [Accepted: 04/19/2022] [Indexed: 11/26/2022] Open
Abstract
Kidney transplantation is the best replacement treatment for the end-stage renal disease. Currently, the imbalance between the number of patients on a transplant list and the number of organs available constitutes the crucial limitation of this approach. To expand the pool of organs amenable for transplantation, kidneys coming from older patients have been employed; however, the combination of these organs in conjunction with the chronic use of immunosuppressive therapy increases the risk of incidence of graft small renal tumors. This narrative review aims to provide the state of the art on the clinical impact and management of incidentally diagnosed small renal tumors in either donors or recipients. According to the most updated evidence, the use of grafts with a small renal mass, after bench table tumor excision, may be considered a safe option for high-risk patients in hemodialysis. On the other hand, an early small renal mass finding on periodic ultrasound-evaluation in the graft should allow to perform a conservative treatment in order to preserve renal function. Finally, in case of a renal tumor in native kidney, a radical nephrectomy is usually recommended.
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Abstract
Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient's journey that maps the experience of living with a kidney transplant and understand the patient's knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients' perspectives.
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Affiliation(s)
- David Al-Adra
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Talal Al-Qaoud
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Kevin Fowler
- The Voice of the Patient, Inc., Columbia, Missouri
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
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19
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Dharia A, Boulet J, Sridhar VS, Kitchlu A. Cancer Screening in Solid Organ Transplant Recipients: A Focus on Screening Liver, Lung, and Kidney Recipients for Cancers Related to the Transplanted Organ. Transplantation 2022; 106:e64-e65. [PMID: 33795594 DOI: 10.1097/tp.0000000000003773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Over the last few decades, the life expectancy of solid organ transplant recipients (SOTRs) has improved significantly. With SOTRs living longer, more recipients are dying from cancer. There is a reported 2- to 3-fold increased risk of cancer-specific mortality in SOTRs compared with the general population. Cancer in an SOTR can be de novo, recurrent, or donor-derived. Cancer screening in this population is crucial, as early detection and treatment may improve outcomes. In the absence of randomized controlled trials dedicated to SOTRs, clinicians rely on clinical practice guidelines from regional and national transplant societies; however, these may vary considerably across jurisdictions and transplanted organ. At present, no widely accepted consensus exists for cancer screening protocols in SOTRs, particularly with regard to screening for malignancy related to transplanted organ. Some SOTRs may be at higher risk of malignancies within the allograft. This is particularly the case in lung and liver recipients, though less common in kidney recipients who are at increased risk of developing renal cell cancer in their native kidneys. This increased risk has not been uniformly incorporated into screening recommendations for SOTRs. In this review, we summarize the cancer screening recommendations for SOTRs from various transplant organizations based on transplanted organ. This review also discusses the complexity and controversies surrounding screening of cancer in the allograft and future avenues to improve cancer detection in this context. More studies specific to SOTRs are required to form generalizable and evidence-based cancer screening guidelines, particularly with respect to cancer screening in the allograft.
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Affiliation(s)
- Atit Dharia
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Jacinthe Boulet
- Division of Cardiology, Department of Medicine, Montreal Heart Institute, Montreal, QC, Canada
| | - Vikas S Sridhar
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
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20
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Cangemi M, Zanussi S, Rampazzo E, Bidoli E, Giunco S, Tedeschi R, Pratesi C, Martorelli D, Casarotto M, Martellotta F, Schioppa O, Serraino D, Steffan A, De Rossi A, Dolcetti R, Vaccher E. Biological Predictors of De Novo Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating TERT mRNA. Front Oncol 2021; 11:772348. [PMID: 34746013 PMCID: PMC8567137 DOI: 10.3389/fonc.2021.772348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 09/30/2021] [Indexed: 11/13/2022] Open
Abstract
Background De novo tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients' immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development. Methods An exploratory longitudinal study was designed based on two serial peripheral blood samples collected at least three months apart. Forty nine SOT patients were selected and stratified by tumor onset during follow-up. Spontaneous T-cell responses to EBV, CMV and tumor associated antigens, EBV-DNA and CMV-DNA loads, and circulating TERT mRNA levels were investigated. Results Significantly higher levels of circulating TERT mRNA were observed 3.5-23.5 months before and close to the diagnosis of cancer as compared to tumor-free patients. Plasmatic TERT mRNA levels >97.73 copies/mL at baseline were significantly associated with the risk of developing de novo tumors (HR=4.0, 95%C.I. = 1.4-11.5, p=0.01). In particular, the risk significantly increased by 4% with every ten-unit increment in TERT mRNA (HR=1.04, 95%C.I. = 1.01-1.07, p=0.01). Conclusions Although obtained in an exploratory study, our data support the importance of identifying early biomarkers of tumor onset in SOT patients useful to modulate the pace of surveillance visits.
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Affiliation(s)
- Michela Cangemi
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Stefania Zanussi
- Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Enrica Rampazzo
- Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy
| | - Ettore Bidoli
- Cancer Epidemiology Unit, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Silvia Giunco
- Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy.,Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology (IOV) - IRCCS, Padova, Italy
| | - Rosamaria Tedeschi
- Microbiology and Virology Unit, "S. Maria degli Angeli" Hospital, Pordenone, Italy
| | - Chiara Pratesi
- Clinical Pathology, "S. Maria degli Angeli" Hospital, Pordenone, Italy
| | - Debora Martorelli
- Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Mariateresa Casarotto
- Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Ferdinando Martellotta
- Division of Medical Oncology A, Centro di Riferimento Oncologico (CRO) Aviano, National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy
| | - Ornella Schioppa
- Division of Medical Oncology A, Centro di Riferimento Oncologico (CRO) Aviano, National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
| | - Anita De Rossi
- Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy.,Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology (IOV) - IRCCS, Padova, Italy
| | - Riccardo Dolcetti
- Centre for Cancer Immunotherapy, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.,Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia.,Faculty of Medicine, The University of Queensland Diamantina Institute, Brisbane, QLD, Australia
| | - Emanuela Vaccher
- Division of Medical Oncology A, Centro di Riferimento Oncologico (CRO) Aviano, National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy
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21
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Abstract
Benefits of solid organ transplantation in end stage organ diseases are indisputable. Malignancy is a feared complication of solid organ transplantation and is a leading cause of mortality in patients with organ transplantation. Iatrogenic immunosuppression to prevent graft rejection plays a crucial role in the cancer development in solid organ transplant recipients. Chronic exposure to immunosuppression increases the malignancy burden through deregulation of host immune defense mechanisms and unchecked proliferation of oncogenic viruses and malignancies associated with these viruses. Vigorous screening of candidates undergoing transplant evaluation for malignancies, careful assessment of donors, and vigilant monitoring of transplant recipients are necessary to prevent, detect, and manage this life-threatening complication.
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22
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Hansen KS, Ghersin H, Piper M, Tavakol M, Lee B, Esserman LJ, Roberts JP, Freise C, Ascher NL, Mukhtar RA. A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines. Am J Transplant 2021; 21:3014-3020. [PMID: 33421310 DOI: 10.1111/ajt.16483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 12/02/2020] [Accepted: 01/01/2021] [Indexed: 01/25/2023]
Abstract
Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.
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Affiliation(s)
- Keith S Hansen
- Division of General Surgery, Department of Surgery, University of California, San Francisco, California
| | - Hila Ghersin
- Division of General Surgery, Department of Surgery, University of California, San Francisco, California
| | - Merisa Piper
- Division of Plastic Surgery, Department of Surgery, University of California, San Francisco, California
| | - Mehdi Tavakol
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California
| | - Brian Lee
- Division of Nephrology, Department of Medicine, University of California, San Francisco, California
| | - Laura J Esserman
- Division of General Surgery, Department of Surgery, University of California, San Francisco, California
| | - John P Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California
| | - Chris Freise
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California
| | - Nancy L Ascher
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California
| | - Rita A Mukhtar
- Division of General Surgery, Department of Surgery, University of California, San Francisco, California
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23
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Abstract
PURPOSE OF REVIEW Kidney and/or pancreas transplantation candidacy criteria have evolved significantly over time reflecting improved pre and post-transplant management. With improvement in medical care, potential candidates for transplant not only are older but also have complex medical issues. This review focuses on the latest trends regarding candidacy for kidney and/or pancreas transplantation along with advances in pretransplant cardiac testing. RECENT FINDINGS More candidates are now eligible for kidney and/or pancreas transplantation owing to less stringent candidacy criteria especially in regards to age, obesity, frailty and history of prior malignancy. Pretransplant cardiovascular assessment has also come a long way with a focus on less invasive strategies to assess for coronary artery disease. SUMMARY Criteria for kidney and/or pancreas transplantation are expanding. Patients who in the past might have been declined because of numerous factors are now finding that transplant centers are more open minded to their candidacy, which could lead to better access to organ transplant wait list.
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Miao K, Zhang L. Application of Immune Checkpoint Inhibitors in Solid Organ Transplantation Recipients: A Systematic Review. Interdiscip Sci 2021; 13:801-814. [PMID: 34152556 DOI: 10.1007/s12539-021-00437-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Solid organ transplantation (SOT) is a treatment method for end-stage organ diseases and improve their life quality, while using long-term immunosuppressant drugs (ISD) is needed to suppress the function of the immune system. Immune checkpoint inhibitors (ICIs) are a class of anti-tumor drugs that kill tumors by activating the autoimmune system. The primary objective of our systematic review is to investigate the risk factors for organ rejection and the efficacy of ICIs in solid organ transplantation recipients (SOTRs). METHODS We searched four databases to find relevant articles up to January 2021. A total of 61 articles involving 106 SOTRs met the screening criteria and were included in our systematic review. The collected data were statistical described, and the risk factors were analyzed by logistic regression. RESULTS Forty-four patients (41.5%) developed host-versus-graft response (HVGR) after ICIs. mTOR inhibitors (pre-ICIs) (p = 0.069, OR = 0.377, 95% CI 0.132-1.078) and calcineurin inhibitors (post-ICIs) (p = 0.056, OR = 0.375, 95%CI 0.137-1.025) may help reduce the incidence of HVGR. Hormones (pre-ICIs) (p = 0.026, OR = 3.150, 95%CI 1.150-8.628) and anti-metabolites (pre-ICIs) (p = 0.022, OR = 3.214, 95%CI 1.185-8.720) may adversely affect the efficacy of ICIs. Only 35.6% of patients both responded well to ICIs treatment and did not develop HVGR. CONCLUSIONS Our systematic review summarizes the use of ICIs in SOTRs and evaluates the efficacy of ICIs and the risk factors that induce HVGR. Through risk factor analysis, we found that mTOR inhibitors and calcineurin inhibitors may help to reduce the occurrence of HVGR; hormones and anti-metabolic drugs may have adverse effects on the efficacy of ICIs. In addition, there is a contradictory relationship between the occurrence of HVGR and the efficacy of ICIs.
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Affiliation(s)
- Kang Miao
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 53 Dongdan North Avenue, Dongcheng District, Beijing, China
| | - Li Zhang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 53 Dongdan North Avenue, Dongcheng District, Beijing, China.
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25
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Williams GJ, Webster AC, Thompson JF. Organ transplantation and outcomes in patients with a past history of melanoma: A systematic review and meta-analysis. Clin Transplant 2021; 35:e14287. [PMID: 33720403 DOI: 10.1111/ctr.14287] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 02/23/2021] [Accepted: 03/08/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of melanoma. AIM To review studies reporting patients with a history of melanoma before solid organ transplantation. METHODS Electronic searches of Medline, Embase, and the Cochrane library up to March 2020. All study designs, in any language and without sample size restriction, were eligible for inclusion. Risk of bias was assessed using established tools, and meta-analysis was performed using a random-effects model. RESULTS We identified 41 studies reporting 703 100 transplant recipients and 1692 had pre-transplantation melanomas. Risk of death, expressed as a hazard ratio, in patients with pre-transplantation melanoma relative to those without prior melanoma, was 1.32 (95% CI: 1.09-1.59). After transplantation, 13.1% of patients with pre-transplantation melanoma developed new or recurrent melanoma (IQR: 4.8%-18.2%). CONCLUSIONS Around 1-in-400 transplant recipients had a prior history of melanoma. This was associated with a greater than 1-in-10 risk of new or recurrent melanoma after transplantation and an increased risk of death. A 5-year waiting time between a melanoma diagnosis and transplantation has been recommended based on historic registry data, but very little additional information is available to justify or revise this.
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Affiliation(s)
| | - Angela C Webster
- School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - John F Thompson
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.,Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
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26
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Al-Adra DP, Hammel L, Roberts J, Woodle ES, Levine D, Mandelbrot D, Verna E, Locke J, D'Cunha J, Farr M, Sawinski D, Agarwal PK, Plichta J, Pruthi S, Farr D, Carvajal R, Walker J, Zwald F, Habermann T, Gertz M, Bierman P, Dizon DS, Langstraat C, Al-Qaoud T, Eggener S, Richgels JP, Chang GJ, Geltzeiler C, Sapisochin G, Ricciardi R, Krupnick AS, Kennedy C, Mohindra N, Foley DP, Watt KD. Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement. Am J Transplant 2021; 21:460-474. [PMID: 32969590 PMCID: PMC8576374 DOI: 10.1111/ajt.16318] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 09/10/2020] [Accepted: 09/10/2020] [Indexed: 01/25/2023]
Abstract
Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.
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Affiliation(s)
- David P Al-Adra
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Laura Hammel
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - John Roberts
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - E Steve Woodle
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | - Deborah Levine
- Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas
| | - Didier Mandelbrot
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Elizabeth Verna
- Department of Medicine, New York-Presbyterian/Columbia, New York, New York
| | - Jayme Locke
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Maryjane Farr
- Department of Medicine, New York-Presbyterian/Columbia, New York, New York
| | - Deirdre Sawinski
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Jennifer Plichta
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Sandhya Pruthi
- Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Deborah Farr
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Richard Carvajal
- Department of Medicine, New York-Presbyterian/Columbia, New York, New York
| | - John Walker
- Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Fiona Zwald
- Piedmont Transplant Institute, Piedmont Atlanta Hospital, Atlanta, Georgia
| | | | - Morie Gertz
- Hematology Division, Mayo Clinic, Rochester, Minnesota
| | - Philip Bierman
- Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska
| | - Don S Dizon
- Lifespan Cancer Institute and Brown University, Providence, Rhode Island
| | - Carrie Langstraat
- Departments of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota
| | - Talal Al-Qaoud
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Scott Eggener
- Department of Urology, University of Chicago, Chicago, Illinois
| | - John P Richgels
- Department of Urology, University of Chicago, Chicago, Illinois
| | - George J Chang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Cristina Geltzeiler
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | | | - Rocco Ricciardi
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Cassie Kennedy
- Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Nisha Mohindra
- Department of Medicine, Northwestern University, Chicago, Illinois
| | - David P Foley
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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27
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Choudhary NS, Saigal S, Saraf N, Soin AS. Extrahepatic Malignancies and Liver Transplantation: Current Status. J Clin Exp Hepatol 2021; 11:494-500. [PMID: 34276155 PMCID: PMC8267344 DOI: 10.1016/j.jceh.2020.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 10/20/2020] [Indexed: 12/12/2022] Open
Abstract
Recipients of liver transplantation (LT) remain at higher risk (adjusted for other risk factors) of de novo malignancies (DNMs). The higher risk can be attributed to the effect of immunosuppression and patient-related risk factors (age, tobacco, alcohol, etiology of liver disease). DNMs are an important cause of late mortality in liver transplant recipients. The pattern (type) of posttransplant malignancies reflects pattern in local population. The common types include skin cancers, solid organ malignancies, and post-transplant lymphoproliferative disorders. Counseling of patients about risk factors and surveillance protocols may help in the prevention and diagnosis at early stage. We also discuss the results of LT in patients with a history of extrahepatic malignancy in the pretransplant period.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Dr Sanjiv Saigal DM, MRCP Senior Director, Hepatology and Liver Transplantation, Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Sector 38, Gurgaon, PIN 122001, India.
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28
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Olimpiadi YB, Brownson KE, Kahn JA, Kim B, Han H, Khemichian S, Fong TL, Kang I, Terando A, Lang JE. Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction. J Surg Res 2020; 256:212-219. [PMID: 32711178 PMCID: PMC7854813 DOI: 10.1016/j.jss.2020.06.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/08/2020] [Accepted: 06/16/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. METHODS We performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. RESULTS Eight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. CONCLUSIONS Surgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.
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Affiliation(s)
- Yuliya B Olimpiadi
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Kirstyn E Brownson
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Jeffrey A Kahn
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Brian Kim
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Hyosun Han
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Saro Khemichian
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Tse-Ling Fong
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Irene Kang
- Division of Medical Oncology, Department of Medicine, University of Southern California, Los Angeles, California
| | - Alicia Terando
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Julie E Lang
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Abstract
Cancer is an important cause of morbidity and mortality after liver transplantation and can occur through three mechanisms: recurrence of a recipient's pre-transplant malignancy, donor-related transmission and de novo development. Currently, the decision to list a patient with a history of malignancy is an individual one. Screening guidelines for potential donors and for recipients after transplant are still widely based on general population guidelines, while the role of chronic immunosuppression remains controversial. These shortcomings mean that patients present at diagnosis with advanced stages of the disease, often precluding curative treatments. The present review summarizes current recommendations for the screening of recipients and donors for pre- and post-transplant malignancies, and current management of recipients who develop cancer after a liver transplant.
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30
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Utilisation de la régression de Poisson en néphrologie. Nephrol Ther 2020; 16:184-190. [DOI: 10.1016/j.nephro.2019.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 09/30/2019] [Indexed: 11/17/2022]
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31
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Watschinger B, Budde K, Crespo M, Heemann U, Hilbrands L, Maggiore U, Mariat C, Oberbauer R, Oniscu GC, Peruzzi L, Sorensen SS, Viklicky O, Abramowicz D. Pre-existing malignancies in renal transplant candidates-time to reconsider waiting times. Nephrol Dial Transplant 2020; 34:1292-1300. [PMID: 30830155 DOI: 10.1093/ndt/gfz026] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 12/24/2018] [Indexed: 12/12/2022] Open
Abstract
Current proposals for waiting times for a renal transplant after malignant disease may not be appropriate. New data on malignancies in end-stage renal disease and recent diagnostic and therapeutic options should lead us to reconsider our current practice.
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Affiliation(s)
- Bruno Watschinger
- Department of Nephrology, Medical University of Vienna, Vienna, Austria
| | - Klemens Budde
- Department of Nephrology, Charité Medical University Berlin, Berlin, Germany
| | - Marta Crespo
- Department of Nephrology, Hospital del Mar, Barcelona, Spain; Institute Mar for Medical Research, Parc de Salut Mar, Barcelona, Spain
| | - Uwe Heemann
- Department of Nephrology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Luuk Hilbrands
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Umberto Maggiore
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Christophe Mariat
- Department of Nephrology, Dialysis, and Renal Transplantation, University North Hospital, Saint Etienne, France
| | - Rainer Oberbauer
- Department of Nephrology, Medical University of Vienna, Vienna, Austria
| | | | - Licia Peruzzi
- Pediatric Nephrology Unit, Regina Margherita Children's Hospital, Turin, Italy
| | - Søren S Sorensen
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Ondrej Viklicky
- Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Daniel Abramowicz
- Department of Nephrology, Antwerp University Hospital, Antwerp University, Antwerp, Belgium
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32
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Livingston-Rosanoff D, Foley DP, Leverson G, Wilke LG. Impact of Pre-Transplant Malignancy on Outcomes After Kidney Transplantation: United Network for Organ Sharing Database Analysis. J Am Coll Surg 2019; 229:568-579. [PMID: 31666186 PMCID: PMC6879822 DOI: 10.1016/j.jamcollsurg.2019.06.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 06/06/2019] [Accepted: 06/06/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Kidney transplant recipients with a history of a pre-transplant malignancy (pre-TM) have an increased risk of post-transplant malignancies (post-TM) and suspected inferior long-term outcomes. No large database studies have examined modern day trends and outcomes in this patient population compared with those without a pre-TM. STUDY DESIGN The United Network for Organ Sharing (UNOS) database was queried for primary adult kidney transplant recipients with pre-TM. Outcomes were compared in patients with and without pre-TM from 2004 to 2016 using multivariable Cox proportional hazard analyses (n = 170,684). RESULTS The rate of kidney transplants in patients with pre-TM increased from <1% of all kidney transplants in 1994 (n = 77) to 8.3% in 2016 (n = 1,329). Pre-TM was associated with development of post-TM (hazard ratio [HR] 1.77 CI 1.68, 1.86), all cause (HR 1.22 CI 1.18, 1.27), and death-censored graft failure (HR 1.08 CI 1.02, 1.15) between 2004 and 2016. The 5-year all cause graft failure rate was 28% for pre-TM patients and 22% for non-pre-TM patients. Pre-TM was associated with decreased patient survival (5-year 80% vs 88% and HR 1.23 CI 1.18, 1.28). Of the deceased, more pre-TM patients died of malignancy (19% vs 11%). CONCLUSIONS Increasing numbers of patients with pre-TM are undergoing kidney transplantation. This analysis indicates that patients with pre-TM are at increased risk of post-TM, graft loss, and decreased overall survival. The study's limitations highlight the need for collaborative database development between transplant and cancer registries to better define the inter-relationship between a pre-TM and cancer survivorship vs freedom from prolonged dialysis.
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Affiliation(s)
| | - David P Foley
- Division of Transplantation, Department of Surgery, University of Wisconsin, Madison, WI
| | - Glen Leverson
- Division of Transplantation, Department of Surgery, University of Wisconsin, Madison, WI
| | - Lee G Wilke
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI
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33
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Park B, Yoon J, Choi D, Kim HJ, Jung YK, Kwon OJ, Lee KG. De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data. Sci Rep 2019; 9:17202. [PMID: 31748582 PMCID: PMC6868238 DOI: 10.1038/s41598-019-53163-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 10/16/2019] [Indexed: 12/20/2022] Open
Abstract
The cancer risk among solid organ transplantation recipients in East-Asia has been insufficiently studied. This study estimated de novo cancer incidence in kidney and liver recipients 2008-2015, compared with the general population in Korea using nationwide data. This is a retrospective cohort study using nationwide health insurance claims data. The study population was comprised of cancer-free 10,085 kidney recipients and 3,822 liver recipients. Standardized incidence ratio (SIR) of cancer using indirect standardization was calculated. Compared with the general population, the cancer risk increased by 3.19-fold in male and 2.56-fold in female kidney recipients. By cancer type, a notably increased SIR was observed for Kaposi sarcoma, renal cancer, skin cancer, and non-Hodgkin's lymphoma in male and for bladder cancer, renal cancer, and non-Hodgkin's lymphoma in female kidney recipients. In liver recipients, the SIR of all cancers was 3.43 in males and 2.30 in females. In male liver recipients, the SIRs for Kaposi sarcoma, non-Hodgkin's lymphoma, myeloid leukemia, and skin cancer and in female recipients those for non-Hodgkin's lymphoma and liver cancer were prominent. A greatly higher SIRs for overall cancer and non-Hodgkin's lymphoma in kidney and liver recipients aged 0-19 were observed, compared with recipients in other age group. The incidence of de novo cancer in kidney and liver recipients was higher than the general population and common types were different. Strategies of cancer prevention and screening after kidney and liver transplantation should be developed in response to the incidence of common types of de novo cancers.
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Affiliation(s)
- Boyoung Park
- Department of Medicine, College of Medicine, Hanyang University, Seoul, South Korea
| | - Junghyun Yoon
- Graduate School of Public Health, Hanyang University, Seoul, South Korea
| | - Dongho Choi
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea. .,Hanyang ICT fusion medical research center, Seoul, South Korea.
| | - Han Joon Kim
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Yun Kyung Jung
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea.,Hanyang ICT fusion medical research center, Seoul, South Korea
| | - Oh Jung Kwon
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Kyeong Geun Lee
- Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea
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34
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Lim WH, Au E, Krishnan A, Wong G. Assessment of kidney transplant suitability for patients with prior cancers: is it time for a rethink? Transpl Int 2019; 32:1223-1240. [PMID: 31385629 PMCID: PMC6900036 DOI: 10.1111/tri.13486] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/16/2019] [Accepted: 07/31/2019] [Indexed: 12/19/2022]
Abstract
Kidney transplant recipients have up to a 100-fold greater risk of incident cancer compared with the age/sex-matched general population, attributed largely to chronic immunosuppression. In patients with a prior history of treated cancers, the type, stage and the potential for cancer recurrence post-transplant of prior cancers are important factors when determining transplant suitability. Consequently, one of the predicaments facing transplant clinicians is to determine whether patients with prior cancers are eligible for transplantation, balancing between the accelerated risk of death on dialysis, the projected survival benefit and quality of life gains with transplantation, and the premature mortality associated with the potential risk of cancer recurrence post-transplant. The guidelines informing transplant eligibility or screening and preventive strategies against cancer recurrence for patients with prior cancers are inconsistent, underpinned by uncertain evidence on the estimates of the incidence of cancer recurrence and the lack of stage-specific outcomes data, particularly among those with multiple myeloma or immune-driven malignancies such as melanomas. With the advent of newer anti-cancer treatment options, it is unclear whether the current guidelines for those with prior cancers remain appropriate. This review will summarize the uncertainties of evidence informing the current recommendations regarding transplant eligibility of patients with prior cancers.
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Affiliation(s)
- Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.,School of Medicine, University of Western Australia, Perth, WA, Australia
| | - Eric Au
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Anoushka Krishnan
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
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35
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Abstract
Cancer is the second most common cause of mortality and morbidity in kidney transplant recipients after cardiovascular disease. Kidney transplant recipients have at least a twofold higher risk of developing or dying from cancer than the general population. The increased risk of de novo and recurrent cancer in transplant recipients is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity. Transplant candidates and potential donors should be screened for cancer as part of the assessment process. For potential recipients with a prior history of cancer, waiting periods of 2-5 years after remission - largely depending on the cancer type and stage of initial cancer diagnosis - are recommended. Post-transplantation cancer screening needs to be tailored to the individual patient, considering the cancer risk of the individual, comorbidities, overall prognosis and the screening preferences of the patient. In kidney transplant recipients diagnosed with cancer, treatment includes conventional approaches, such as radiotherapy and chemotherapy, together with consideration of altering immunosuppression. As the benefits of transplantation compared with dialysis in potential transplant candidates with a history of cancer have not been assessed, current clinical practice relies on evidence from observational studies and registry analyses.
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Affiliation(s)
- Eric Au
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia.,Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia
| | - Jeremy R Chapman
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia.
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36
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Pretransplant Cancer in Kidney Recipients in Relation to Recurrent and De Novo Cancer Incidence Posttransplantation and Implications for Graft and Patient Survival. Transplantation 2019; 103:581-587. [PMID: 30418430 DOI: 10.1097/tp.0000000000002459] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Whether kidney transplant recipients who were treated for a malignant tumor before transplantation are at an increased risk of developing a tumor posttransplantation has not been adequately quantified and characterized. METHODS We studied more than 270 000 patients on whom pretransplant and posttransplant malignancy data were reported to the Collaborative Transplant Study. More than 4000 of these patients were treated for pretransplant malignancy. The posttransplant tumor incidence in these patients was compared to that in recipients without a pretransplant tumor. Cox regression, considering multiple confounders, was applied. RESULTS Significant increases in posttransplant tumor incidence with hazard ratio ranging from 2.10 to 5.47 (all P < 0.001) were observed for tumors in the site-specific pretransplant locations, suggesting tumor recurrences. There were also significantly increased de novo tumors in new locations with hazard ratio ranging from 1.28 to 1.89. Pretransplant basal cell carcinoma of the skin and male genital cancer were associated with significantly increased death-censored graft survival, suggesting impaired immune responsiveness against transplanted kidneys. Time interval from pretransplant tumor occurrence to transplantation and posttransplant mammalian target of rapamycin inhibitor treatment was not found to be of significant relevance in this study. CONCLUSIONS Patients who experienced a pretransplant tumor are at significant risk of tumor recurrence, regardless of the length of interval between tumor treatment and transplantation. There is also some increased risk for de novo tumors, suggesting impaired immune surveillance. Impaired tumor immunity appears to extend to a lower rate of transplant rejection because patients with pretransplant tumors tended to show improved death-censored graft survival.
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Bierman PJ. Solid Organ Transplantation in Patients With a History of Lymphoma. J Oncol Pract 2018; 14:11-17. [DOI: 10.1200/jop.2017.028480] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
There is an increasing number of long-term survivors of Hodgkin and non-Hodgkin lymphoma. These people may have a need for subsequent solid organ transplantation, often as a result of late effects of their lymphoma treatment. There is abundant literature demonstrating that patients with a history of lymphoma are appropriate candidates for solid organ transplantation. Long-term survival without relapse and with a functioning graft is possible. Patients with a history of post-transplantation lymphoproliferative disorders and patients who have received a prior hematopoietic stem-cell transplantation may also be candidates. Although high-level supporting evidence is not available, most guidelines recommend a waiting period of 2 to 5 years after lymphoma treatment before patients undergo solid organ transplantation. Each patient with a history of lymphoma requires a multidisciplinary approach and should be evaluated on a case-by-case basis before consideration of solid organ transplantation.
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