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Turra V, Manzi J, Rombach S, Zaragoza S, Ferreira R, Guerra G, Conzen K, Nydam T, Livingstone A, Vianna R, Abreu P. Donors With Previous Malignancy: When Is It Safe to Proceed With Organ Transplantation? Transpl Int 2025; 38:13716. [PMID: 39926359 PMCID: PMC11802283 DOI: 10.3389/ti.2025.13716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 01/07/2025] [Indexed: 02/11/2025]
Abstract
The growing number of organ donors in the United States, from 14,011 in 2012 to 21,374 in 2022, highlights progress in addressing the critical issue of organ shortages. However, the demand remains high, with 17 patients dying daily while on the waiting list. As of August 2023, over 103,544 individuals are awaiting transplants, predominantly for kidneys (85.7%). To expand the donor pool, the inclusion of elderly donors, including those with a history of malignancies, is increasingly considered. In 2022, 7% of all donors were aged 65 and above, despite the complexities their medical histories may introduce, particularly the risk of donor-transmitted cancer (DTC). This review examines the challenges and potential benefits of using donors with known malignancy histories, balancing the risks of DTC against the urgency for transplants. A critical analysis is presented on current knowledge and the decision-making processes that consider cancer types, stages, and patient survival outcomes. The goal is to identify missed opportunities and improve strategies for safe and effective organ transplantation from this donor demographic.
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Affiliation(s)
- Vitor Turra
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Joao Manzi
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Sarah Rombach
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Simone Zaragoza
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Raphaella Ferreira
- HCA Healthcare–HealthOne Internal Medicine Residency Program, Sky Ridge Medical Center, Denver, CO, United States
| | - Giselle Guerra
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Kendra Conzen
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Trevor Nydam
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Alan Livingstone
- Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States
| | - Rodrigo Vianna
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL, United States
| | - Phillipe Abreu
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
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Villani V, Kulkarni RD, Fair JH, Shanmugarajah K. Kidney Transplantation From Donors With Malignant Renal Masses: A Systematic Review. Clin Transplant 2024; 38:e70020. [PMID: 39512121 DOI: 10.1111/ctr.70020] [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: 09/10/2024] [Revised: 10/10/2024] [Accepted: 10/22/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND Small malignant renal tumors can be found in up to 1.3% of kidney donors. Several studies have investigated the use of these kidneys for transplantation, after ex vivo resection of the malignant mass. METHODS We performed a systematic review of the literature on PubMed, Embase, and Web of Science of studies including reports of malignant renal masses excised from kidney grafts prior to transplantation. Articles including benign pathology only were excluded. RESULTS Our search strategy identified 226 patients over 32 studies. Pathology included 107 clear cell carcinomas, 27 papillary renal cell carcinomas (RCCs), 84 other types of RCCs, and 8 transitional cell carcinomas. The majority of cancers were grade 1 or 2 (81.6%). Average tumor size was 12.6 mm. Clavien-Dindo ≥ 3 complication rate was 22%. Mean follow-up was 39.9 months. The 1-year, 3-year, and 5-year overall survival rate for recipients of living donor grafts was 95.8%, 92.1%, and 75.1%. The 1-year, 3-year, and 5-year living donor death-censored graft survival rate was 90.8, 85.2%, and 64.8%. Of the 226 patients, 6 (2.7%) experienced a malignant recurrence. The average time to recurrence was 36.1 months. CONCLUSIONS Transplantation of kidney grafts after resection of small cancerous masses is relatively safe and has low rates of recurrent malignancy. In the case of a living donor, appropriate counseling on partial nephrectomy versus donor nephrectomy should be provided, ideally by a surgeon who is not part of the transplant team. Recipients of these grafts should be carefully selected and counseled regarding the additional potential technical and oncological risks.
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Affiliation(s)
- Vincenzo Villani
- Division of Immunology and Organ Transplantation, Department of Surgery, McGovern Medical School at UTHealth Houston, Houston, Texas, USA
| | - Rupak D Kulkarni
- Division of Immunology and Organ Transplantation, Department of Surgery, McGovern Medical School at UTHealth Houston, Houston, Texas, USA
| | - Jeffrey H Fair
- Division of Immunology and Organ Transplantation, Department of Surgery, McGovern Medical School at UTHealth Houston, Houston, Texas, USA
| | - Kumaran Shanmugarajah
- Department of Surgery, Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
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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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Malvi D, Vasuri F, Albertini E, Carbone M, Novelli L, Mescoli C, Cardillo M, Pagni F, D'Errico A, Eccher A. Donors risk assessment in transplantation: From the guidelines to their real-world application. Pathol Res Pract 2024; 255:155210. [PMID: 38422913 DOI: 10.1016/j.prp.2024.155210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/08/2024] [Accepted: 02/11/2024] [Indexed: 03/02/2024]
Abstract
Transplantation of an organ from a donor carries an unavoidable risk of tumor transmission. The need to extend the donor pool increases the use of organs from donors with malignancies and potential disease transmission is a constant tension influencing donor suitability decisions. Current classification systems for the assessment of donor malignancy transmission risk have evolved from reports of potential transmission events in recipients to national donation and transplant surveillance agencies. Although the risk of malignancy transmission is very low in the general transplant setting it must constantly be balanced with the transplant benefits. Guidelines are mainly based on large registries and sparse case reports of transmission, so they cannot cover all the possible situations. For this reason, in 2004 in Italy, the National Transplant Center gave rise to the Second Opinion Service, charged by the Ministry of Health, by structuring expertise in diagnostic oncology and risk transmission and making it available to the Italian Transplant Centers. In this paper the registry of the Italian Oncological Second Opinion was reviewed, from 2016 to 2018, to detail the most frequent and problematic neoplastic topics addressed, those are separately reported and discussed. Furthermore, a review of the most recent strategies and risk stratification is provided, according to the most recent literature evidence and to the European Guidelines.
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Affiliation(s)
- Deborah Malvi
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Elisa Albertini
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; School of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Maurizio Carbone
- University Milan Bicocca, Department of Medicine and Surgery, Departmental Center of Digital Medicine, Milan, Italy
| | - Luca Novelli
- Institute of Histopathology and Molecular Diagnosis, Careggi University Hospital, Florence, Italy
| | - Claudia Mescoli
- Surgical Pathology and Cytopathology Unit, Department of Medicine, University and Hospital Trust of Padua, Italy
| | - Massimo Cardillo
- Italian National Transplantation Center, Italian National Institute of Health, Rome, Italy
| | - Fabio Pagni
- University Milan Bicocca, Department of Medicine and Surgery, Departmental Center of Digital Medicine, Milan, Italy
| | - Antonia D'Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.
| | - Albino Eccher
- Section of Pathology, Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, University Hospital of Modena, Modena, Italy
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Kawashima S, Joachim K, Abdelrahim M, Abudayyeh A, Jhaveri KD, Murakami N. Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates. KOREAN JOURNAL OF TRANSPLANTATION 2022; 36:82-98. [PMID: 35919193 PMCID: PMC9296977 DOI: 10.4285/kjt.22.0013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 11/22/2022] Open
Abstract
Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.
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Affiliation(s)
- Shun Kawashima
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Kole Joachim
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX, USA
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kenar D. Jhaveri
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell, Great Neck, NY, USA
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| | - Naoka Murakami
- Transplantation Research Center, Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Mahíllo B, Martín S, Molano E, Navarro A, Castro P, Pont T, Andrés A, Galán J, López M, Oliver E, Martínez A, Mosteiro F, Roque R, Pérez-Redondo M, Cid-Cumplido M, Ballesteros MA, Daga D, Quindós B, Sancho M, Royo-Villanova M, Bernabé E, Muñoz R, Chacón JI, Coll E, Domínguez-Gil B. Malignancies in Deceased Organ Donors: The Spanish Experience. Transplantation 2022; 106:1814-1823. [DOI: 10.1097/tp.0000000000004117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Domínguez-Gil B, Moench K, Watson C, Serrano MT, Hibi T, Asencio JM, Van Rosmalen M, Detry O, Heimbach J, Durand F. Prevention and Management of Donor-transmitted Cancer After Liver Transplantation: Guidelines From the ILTS-SETH Consensus Conference. Transplantation 2022; 106:e12-e29. [PMID: 34905759 DOI: 10.1097/tp.0000000000003995] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
As with any other intervention in health, liver transplantation (LT) entails a variety of risks, including donor-transmitted cancers (DTCs). At present, 2%-4% of used deceased organ donors are known to have a current or past history of malignancy. The frequency of DTCs is consistently reported at 3-6 cases per 10 000 solid organ transplants, with a similar frequency in the LT setting. A majority of DTCs are occult cancers unknown in the donor at the time of transplantation. Most DTCs are diagnosed within 2 y after LT and are associated with a 51% probability of survival at 2 y following diagnosis. The probability of death is greatest for DTCs that have already metastasized at the time of diagnosis. The International Liver Transplantation Society-Sociedad Española de Trasplante Hepático working group on DTC has provided guidance on how to minimize the occurrence of DTCs while avoiding the unnecessary loss of livers for transplantation both in deceased and living donor LT. The group endorses the Council of Europe classification of risk of transmission of cancer from donor to recipient (minimal, low to intermediate, high, and unacceptable), classifies a range of malignancies in the liver donor into these 4 categories, and recommends when to consider LT, mindful of the risk of DTCs, and the clinical condition of patients on the waiting list. We further provide recommendations to professionals who identify DTC events, stressing the need to immediately alert all stakeholders concerned, so a coordinated investigation and management can be initiated; decisions on retransplantation should be made on a case-by-case basis with a multidisciplinary approach.
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Affiliation(s)
| | - Kerstin Moench
- Donor Transplant Coordination Unit, Westpfalz-Klinikum, Kaiserslautern, Germany
| | - Christopher Watson
- The Roy Calne Transplant Unit and Department of Surgery, University of Cambridge, Cambridge, United Kingdom
| | - M Trinidad Serrano
- Hepatology Section, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - José M Asencio
- Liver Transplant Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, Centre Hospitalier Universitaire de Liege, University of Liege, Liege, Belgium
| | | | - François Durand
- Hepatology Department, Liver Intensive Care Unit, Hospital Beaujon, Clichy, France
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Kaul DR, Vece G, Blumberg E, La Hoz RM, Ison MG, Green M, Pruett T, Nalesnik MA, Tlusty SM, Wilk AR, Wolfe CR, Michaels MG. Ten years of donor-derived disease: A report of the disease transmission advisory committee. Am J Transplant 2021; 21:689-702. [PMID: 32627325 DOI: 10.1111/ajt.16178] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/21/2020] [Accepted: 06/19/2020] [Indexed: 01/25/2023]
Abstract
Despite clinical and laboratory screening of potential donors for transmissible disease, unexpected transmission of disease from donor to recipient remains an inherent risk of organ transplantation. The Disease Transmission Advisory Committee (DTAC) was created to review and classify reports of potential disease transmission and use this information to inform national policy and improve patient safety. From January 1, 2008 to December 31, 2017, the DTAC received 2185 reports; 335 (15%) were classified as a proven/probable donor transmission event. Infections were transmitted most commonly (67%), followed by malignancies (29%), and other disease processes (6%). Forty-six percent of recipients receiving organs from a donor that transmitted disease to at least 1 recipient developed a donor-derived disease (DDD). Sixty-seven percent of recipients developed symptoms of DDD within 30 days of transplantation, and all bacterial infections were recognized within 45 days. Graft loss or death occurred in about one third of recipients with DDD, with higher rates associated with malignancy transmission and parasitic and fungal diseases. Unexpected DDD was rare, occurring in 0.18% of all transplant recipients. These findings will help focus future efforts to recognize and prevent DDD.
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Affiliation(s)
- Daniel R Kaul
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Gabe Vece
- United Network for Organ Sharing, Richmond, Virginia, USA
| | - Emily Blumberg
- Department of Internal Medicine, Division of Infectious Disease, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ricardo M La Hoz
- Division of Infectious Disease and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Michael G Ison
- Divisions of Infectious Disease and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael Green
- Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Timothy Pruett
- Division of Transplantation, Department of Surgery, University of Minneapolis, Minneapolis, Minnesota, USA
| | - Michael A Nalesnik
- Division of Hepatic and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Susan M Tlusty
- United Network for Organ Sharing, Richmond, Virginia, USA
| | - Amber R Wilk
- United Network for Organ Sharing, Richmond, Virginia, USA
| | - Cameron R Wolfe
- Department of Internal Medicine, Division of Infectious Diseases, Duke University Medical School, Durham, North Carolina, USA
| | - Marian G Michaels
- Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Ambrosi F, Ricci C, Malvi D, Cillia CD, Ravaioli M, Fiorentino M, Cardillo M, Vasuri F, D'Errico A. Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors. Kidney Res Clin Pract 2020; 39:487-494. [PMID: 32855366 PMCID: PMC7770991 DOI: 10.23876/j.krcp.20.050] [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: 04/06/2020] [Revised: 07/09/2020] [Accepted: 07/13/2020] [Indexed: 11/10/2022] Open
Abstract
Background We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.
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Affiliation(s)
- Francesca Ambrosi
- Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Costantino Ricci
- Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Deborah Malvi
- Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Carlo De Cillia
- Emilia-Romagna Transplant Reference Centre, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Matteo Ravaioli
- Transplant Surgery Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | | | | | - Francesco Vasuri
- Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Antonia D'Errico
- Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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