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Aizman L, Pakhchanian H, Barata Herrera D, Bibee K, Loss M. Top 50 Most Cited Articles in Transplant Dermatology: A Bibliometric Analysis. Dermatol Surg 2025; 51:365-369. [PMID: 39530507 DOI: 10.1097/dss.0000000000004486] [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: 11/16/2024]
Abstract
BACKGROUND Solid organ transplant recipients are at high risk for developing skin malignancies due to prolonged immunosuppression. The field of transplant dermatology (TD) has experienced a surge in research and clinical advancements, yet there is no quantitative evaluation estimating the impact of TD literature. OBJECTIVE Identify and characterize the most frequently cited TD articles. METHODS Institute For Scientific Information Web of Science was used to identify the 50 most cited research articles in TD. Results were reviewed by 3 independent authors. A network analysis was performed to assess collaboration patterns among coauthors. RESULTS Top articles held a combined total of 12,114 citations. The top-cited article was "Cancer incidence before and after kidney transplantation," by Vajdic and colleagues in the Journal of the American Medical Association (2006) with 872 citations. A total of 22 countries and 221 institutions were represented. CONCLUSION This bibliometric analysis offers a detailed overview of the most cited manuscripts in TD and illustrates the discoveries steering TD research and practice.
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Affiliation(s)
- Leora Aizman
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Haig Pakhchanian
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
| | - Daniela Barata Herrera
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kristin Bibee
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Manisha Loss
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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2
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Romano L, Caponio C, Vistoli F, Lupi E, Fargnoli MC, Esposito M, Lancione L, Bellobono M, Hassan T, Iacobelli E, Semproni L, Panarese A. Management of Cutaneous Squamous Cell Carcinoma of the Scalp in Kidney Transplant Recipients. Cancers (Basel) 2025; 17:1113. [PMID: 40227637 PMCID: PMC11987857 DOI: 10.3390/cancers17071113] [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: 01/20/2025] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Organ transplant recipients are at a significantly higher risk of developing skin cancer compared to the general population, particularly cutaneous squamous cell carcinoma. Approximately 3-8% of these carcinomas are located on the scalp. Scalp reconstruction is particularly challenging, especially for large excisions, due to the thickness of the scalp, the inelastic aponeurosis of the galea, and the integrity of the hair-bearing scalp. Additionally, in organ transplant recipients, the presence of numerous comorbidities and the increased risk of infection due to immunosuppressive therapy make management more complex. Based on our experience and the existing literature, we aim to describe possible reconstruction methods and discuss the combined management of medical and immunosuppressive therapy. METHOD We present our experience with seven kidney transplant patients who underwent excision of cutaneous squamous cell carcinoma with a diameter larger than 3 cm. The crane technique involves three key steps. First, the tumor is excised with wide margins of disease-free tissue. Next, a pericranial flap is rotated and positioned to cover the exposed cranial bone. Finally, a bilayer dermal substitute is applied to create a microenvironment that supports skin graft implantation. RESULTS The crane technique was used for six patients. In one case, an O-Z rotation flap was used. All patients modified their immunosuppressive therapy, with those receiving antiproliferative therapy switching everolimus after surgery. CONCLUSIONS When combined with a post-operative modification of the immunosuppressive regimen, the crane technique could be considered a feasible, safe, and effective approach to managing large cSCC of the scalp in fragile patients.
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Affiliation(s)
- Lucia Romano
- Department of General and Transplant Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (L.R.); (F.V.); (L.L.); (M.B.)
| | - Chiara Caponio
- UOSD of General and Oncological Dermatology, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (C.C.); (M.E.)
| | - Fabio Vistoli
- Department of General and Transplant Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (L.R.); (F.V.); (L.L.); (M.B.)
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
| | - Ettore Lupi
- Department of Maxillo-Facial Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy;
| | | | - Maria Esposito
- UOSD of General and Oncological Dermatology, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (C.C.); (M.E.)
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
| | - Laura Lancione
- Department of General and Transplant Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (L.R.); (F.V.); (L.L.); (M.B.)
| | - Manuela Bellobono
- Department of General and Transplant Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (L.R.); (F.V.); (L.L.); (M.B.)
| | - Tarek Hassan
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
| | - Elisabetta Iacobelli
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
| | - Luca Semproni
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
| | - Alessandra Panarese
- Department of General and Transplant Surgery, San Salvatore Hospital, ASL1 Abruzzo, Coppito, 67100 L’Aquila, Italy; (L.R.); (F.V.); (L.L.); (M.B.)
- Department of Biotechnological and Applied Clinical Sciences, Via Giuseppe Petrini, University of L’Aquila, Coppito, 67100 L’Aquila, Italy; (T.H.); (E.I.); (L.S.)
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Khan MA, Hanna A, Sridhara S, Chaudhari H, Me HM, Attieh RM, Abu Jawdeh BG. Maintenance Immunosuppression in Kidney Transplantation: A Review of the Current Status and Future Directions. J Clin Med 2025; 14:1821. [PMID: 40142628 PMCID: PMC11943253 DOI: 10.3390/jcm14061821] [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: 02/06/2025] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Kidney transplantation remains the gold standard for managing end-stage kidney disease, providing superior survival and quality-of-life outcomes compared to dialysis. Despite the ongoing gap between organ availability and demand, it is inevitable that kidney transplantation will continue to grow. This is owed to broader organ sharing, increased comfort of transplant programs with marginal kidney utilization, and the expansion of paired exchange among living donor kidneys. The evolution of kidney transplantation could not have been possible without the availability of effective immunosuppressive regimens that prevent rejection and maintain graft function. Mycophenolic acid and calcineurin inhibitors continue to serve as the foundation of modern maintenance immunosuppression. While these agents have markedly reduced acute rejection rates, their long-term efficacy in graft survival remains suboptimal. Alternative immunosuppressive therapies, including belatacept and mammalian target of rapamycin inhibitors, have demonstrated potential benefits. However, concerns regarding an increased risk of rejection have limited their widespread adoption as primary treatment options. In addition to ongoing efforts to refine steroid- and calcineurin inhibitor-sparing strategies, the identification of practical and quantifiable biomarkers for predicting long-term graft survival remains a critical objective. This review evaluates contemporary immunosuppressive protocols, highlights existing challenges, and explores future directions for optimizing long-term transplant outcomes.
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Affiliation(s)
- Muhammad Ali Khan
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Alessandra Hanna
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Srilekha Sridhara
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Harshad Chaudhari
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Hay Me Me
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
| | - Rose Mary Attieh
- Department of Transplant, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Bassam G. Abu Jawdeh
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, 5777 E. Mayo Blvd, Phoenix, AZ 85054, USA; (A.H.); (S.S.); (H.C.); (H.M.M.)
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4
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Struckmeier AK, Gosau M, Smeets R. Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies. Transplant Rev (Orlando) 2024; 38:100882. [PMID: 39348772 DOI: 10.1016/j.trre.2024.100882] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.
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Affiliation(s)
- Ann-Kristin Struckmeier
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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5
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Erard D, Steiner A, Boillot O, Thimonier E, Vallin M, Veyre F, Guillaud O, Radenne S, Dumortier J. Calcineurin-Inhibitor Discontinuation Could Reduce the Risk of De Novo Malignancies After Liver Transplantation for Alcohol-Related Liver Disease. Clin Transplant 2024; 38:e70014. [PMID: 39552184 DOI: 10.1111/ctr.70014] [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: 01/05/2024] [Revised: 05/29/2024] [Accepted: 10/14/2024] [Indexed: 11/19/2024]
Abstract
BACKGROUND De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol-related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation. METHODS From 1990 to 2015, all patients transplanted for ALD were included. RESULTS A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years. CONCLUSION Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non-modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD.
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Affiliation(s)
- Domitille Erard
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Anouk Steiner
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Olivier Boillot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Lyon, France
| | - Elsa Thimonier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Mélanie Vallin
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Florian Veyre
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Olivier Guillaud
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Sylvie Radenne
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Jérôme Dumortier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Lyon, France
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Liu X, Shen J, Yan H, Hu J, Liao G, Liu D, Zhou S, Zhang J, Liao J, Guo Z, Li Y, Yang S, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Luo P, Zhao M, Liu Y. Posttransplant complications: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2024; 5:e669. [PMID: 39224537 PMCID: PMC11366828 DOI: 10.1002/mco2.669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.
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Affiliation(s)
- Xiaoyou Liu
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Junyi Shen
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hongyan Yan
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jianmin Hu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Guorong Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ding Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Song Zhou
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jie Zhang
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jun Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Zefeng Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yuzhu Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Siqiang Yang
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Shichao Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hua Chen
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ying Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Min Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Lipei Fan
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Liuyang Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Peng Luo
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ming Zhao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yongguang Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
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Abu Jawdeh BG, Me HM. Immunosuppression in Kidney Transplant Recipients: An Update for the General Nephrologist. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:408-415. [PMID: 39232611 DOI: 10.1053/j.akdh.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 04/29/2024] [Accepted: 05/02/2024] [Indexed: 09/06/2024]
Abstract
Over the last 7 decades, kidney transplantation has evolved from an experiment between identical twins to becoming the gold standard treatment for end-stage kidney disease. To date, mycophenolate and calcineurin inhibitors, with or without prednisone, continue to constitute the backbone of modern maintenance immunosuppression. Despite major strides in improving acute rejection, long-term outcomes remain suboptimal with current regimens. Alternatives to calcineurin inhibitors such as belatacept and mammalian targets of rapamycin inhibitors exist; however, their wider-scale adoption remains relatively delayed due to concerns about increased rejection rates. In addition to continuing the investigation of steroid and calcineurin inhibitor sparing protocols, it is time to identify measurable surrogates for meaningful long-term graft survival. iBOX, a dynamic risk-prediction tool that predicts long-term death-censored graft failure could be a potential surrogate end point for future immunosuppression clinical trials. In this review, we summarize the landmark studies supporting current immunosuppression protocols and briefly discuss challenges and future directions.
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Affiliation(s)
| | - Hay Me Me
- Division of Nephrology and Hypertension, Mayo Clinic Arizona, Phoenix, AZ
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8
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Niinimäki P, Siuko M, Tynninen O, Kivelä TT, Uusitalo M. Cutaneous squamous cell carcinoma of the eyelid in northern latitudes, a 25-year experience in Finland. Acta Ophthalmol 2024; 102:535-543. [PMID: 38057922 DOI: 10.1111/aos.15819] [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: 08/08/2023] [Revised: 10/10/2023] [Accepted: 11/06/2023] [Indexed: 12/08/2023]
Abstract
PURPOSE To evaluate the incidence, clinical features, diagnostic challenges, management and prognosis of cutaneous squamous cell carcinoma of the eyelid (ecSCC) in southern Finland, northern Europe, latitude 62° N. METHODS Patients were identified from the Finnish Cancer Registry and the Helsinki University Hospital databases during a 25-year period (1998-2022). Age, sex, location, clinical and histopathological diagnosis, treatment and outcome were retrieved. RESULTS Cutaneous squamous cell carcinoma of the eyelid (ecSCC) was diagnosed in 58 patients. The mean age-standardized incidence was 1.03 per 100 000. Median age at the time of histopathological diagnosis was 79 (range 55-93) years; sex ratio was 0.52. Clinical diagnosis in the referral was ecSCC in only three patients. The most frequent misdiagnosis (38%) was basal cell carcinoma (BCC). One or more of the known risk factors (smoking, history of extensive sun exposure, systemic immunosuppression and previous in situ cSCC/cSCC) were documented in 71% of the patients. More than one third (38%) of the patients developed in situ SCC elsewhere on the skin; one third (31%) of the patients had invasive cSCC elsewhere. During the median follow-up time of 24 months, three patients experienced local recurrence, four patients developed metastatic disease (median 19 months) and two patients died of metastatic ecSCC. CONCLUSION The estimated incidence of ecSCC in Finland (predominantly white Caucasian) was higher than in a previous study from Europe. Clinical diagnosis of ecSCC is difficult and often misdiagnosed as BCC. Immunosuppression as a risk factor should noticed. Recurrences of ecSCC, which may be lethal, were infrequent.
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Affiliation(s)
- Paula Niinimäki
- Department of Ophthalmology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Mika Siuko
- Department of Ophthalmology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Olli Tynninen
- Department of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Tero T Kivelä
- Department of Ophthalmology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Marita Uusitalo
- Department of Ophthalmology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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9
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Jiang R, Fritz M, Que SKT. Cutaneous Squamous Cell Carcinoma: An Updated Review. Cancers (Basel) 2024; 16:1800. [PMID: 38791879 PMCID: PMC11119634 DOI: 10.3390/cancers16101800] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024] Open
Abstract
Representing the second most common skin cancer, the incidence and disease burden of cutaneous squamous cell carcinoma (cSCC) continues to increase. Surgical excision of the primary site effectively cures the majority of cSCC cases. However, an aggressive subset of cSCC persists with clinicopathological features that are indicative of higher recurrence, metastasis, and mortality risks. Acceleration of these features is driven by a combination of genetic and environmental factors. The past several years have seen remarkable progress in shaping the treatment landscape for advanced cSCC. Risk stratification and clinical management is a top priority. This review provides an overview of the current perspectives on cSCC with a focus on staging, treatment, and maintenance strategies, along with future research directions.
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Affiliation(s)
- Rina Jiang
- Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Mike Fritz
- Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Syril Keena T. Que
- Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
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10
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Sartain F, Viecelli AK, Veitch M, Franklin ME, Dymock BW, Wells JW, Campbell SB. Predicting Tacrolimus Concentrations in the Skin of Adult Kidney Transplant Recipients: A Feasibility Study. Transpl Int 2024; 37:12019. [PMID: 38323070 PMCID: PMC10844510 DOI: 10.3389/ti.2024.12019] [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: 09/08/2023] [Accepted: 01/11/2024] [Indexed: 02/08/2024]
Abstract
Solid organ transplant recipients are at an increased risk of developing skin cancers due to chronic immunosuppression, particularly with calcineurin inhibitors. Tacrolimus is the most prescribed calcineurin inhibitor in this patient cohort, and understanding tacrolimus concentrations in the skin will facilitate the development of anti-cancer preventive and therapeutic strategies. Here, we show that in mice, tacrolimus blood levels peaked rapidly ∼1 h post last oral dose while skin levels rose more slowly and remained high for at least 6 h. Subsequently, tacrolimus skin and blood concentrations were assessed in 15 kidney transplant recipients. The mean age was 61 years, the average time post-transplant was 7 years (range 0-21 years) and 87% were male. The average skin sampling time post tacrolimus dosing was 6 h 32 min. Skin tacrolimus concentrations ranged from 7.1 ng/g to 71.2 ng/g and correlated with blood concentrations (r = 0.6). Mouse and human mean skin concentrations were in a similar range. Our data suggests that tacrolimus measurements in the blood may be used to approximate tacrolimus concentrations in the skin of kidney transplant recipients, and further exploited for the delivery of anti-cancer therapies designed to antagonize the immunosuppressive effects of tacrolimus in the skin.
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Affiliation(s)
| | - Andrea K. Viecelli
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Margaret Veitch
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Michael E. Franklin
- Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Brian W. Dymock
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, QLD, Australia
| | - James W. Wells
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Dermatology Research Centre, Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Scott B. Campbell
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
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11
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Bellini A, Finocchietti M, Rosa AC, Nordio M, Ferroni E, Massari M, Spila Alegiani S, Masiero L, Bedeschi G, Cardillo M, Lucenteforte E, Piccolo G, Leoni O, Pierobon S, Ledda S, Garau D, Davoli M, Addis A, Belleudi V, on behalf of CESIT study group. Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study. PLoS One 2024; 19:e0295205. [PMID: 38165971 PMCID: PMC10760756 DOI: 10.1371/journal.pone.0295205] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 11/16/2023] [Indexed: 01/04/2024] Open
Abstract
Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.
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Affiliation(s)
- Arianna Bellini
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | | | | | | | | | - Marco Massari
- National Centre for Drug Research and Evaluation, Istituto Superiore Di Sanità, Rome, Italy
| | | | - Lucia Masiero
- Italian National Transplant Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Gaia Bedeschi
- Italian National Transplant Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Massimo Cardillo
- Italian National Transplant Centre, Istituto Superiore di Sanità, Rome, Italy
| | - Ersilia Lucenteforte
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Olivia Leoni
- Department of Health of Lombardy Region, Epidemiology Observatory, Milan, Italy
| | | | - Stefano Ledda
- General Directorate for Health, Sardinia Region, Italy
| | | | - Marina Davoli
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Antonio Addis
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Valeria Belleudi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
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12
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Order KE, Rodig NM. Pediatric Kidney Transplantation: Cancer and Cancer Risk. Semin Nephrol 2024; 44:151501. [PMID: 38580568 PMCID: PMC11734768 DOI: 10.1016/j.semnephrol.2024.151501] [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] [Indexed: 04/07/2024]
Abstract
Children with end-stage kidney disease (ESKD) face a lifetime of complex medical care, alternating between maintenance chronic dialysis and kidney transplantation. Kidney transplantation has emerged as the optimal treatment of ESKD for children and provides important quality of life and survival advantages. Although transplantation is the preferred therapy, lifetime exposure to immunosuppression among children with ESKD is associated with increased morbidity, including an increased risk of cancer. Following pediatric kidney transplantation, cancer events occurring during childhood or young adulthood can be divided into two broad categories: post-transplant lymphoproliferative disorders and non-lymphoproliferative solid tumors. This review provides an overview of cancer incidence, types, outcomes, and preventive strategies in this population.
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Affiliation(s)
- Kaitlyn E Order
- Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Boston, MA
| | - Nancy M Rodig
- Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Boston, MA.
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13
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de Fázio MR, Cristelli MP, Tomimori J, Koga CE, Ogawa MM, Beneventi GT, Tedesco-Silva H, Medina-Pestana J. Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study. J Bras Nefrol 2023; 45:480-487. [PMID: 37565728 PMCID: PMC10726662 DOI: 10.1590/2175-8239-jbn-2023-0013en] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/31/2023] [Indexed: 08/12/2023] Open
Abstract
INTRODUCTION Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. METHODS This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. RESULTS Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. CONCLUSIONS This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
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Affiliation(s)
- Marina Rezende de Fázio
- Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil
| | | | - Jane Tomimori
- Universidade Federal de São Paulo, Divisão de Dermatologia, São Paulo, SP, Brazil
| | - Carlos Eiji Koga
- Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil
| | | | - Giovanni Tani Beneventi
- Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil
| | - Helio Tedesco-Silva
- Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil
| | - José Medina-Pestana
- Universidade Federal de São Paulo, Hospital do Rim, Divisão de Nefrologia, São Paulo, SP, Brazil
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14
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Veitch M, Beaumont K, Pouwer R, Chew HY, Frazer IH, Soyer HP, Campbell S, Dymock BW, Harvey A, Cock TA, Wells JW. Local blockade of tacrolimus promotes T-cell-mediated tumor regression in systemically immunosuppressed hosts. J Immunother Cancer 2023; 11:e006783. [PMID: 37678918 PMCID: PMC10496666 DOI: 10.1136/jitc-2023-006783] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/30/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Immunosuppressive drugs such as tacrolimus have revolutionized our ability to transplant organs between individuals. Tacrolimus acts systemically to suppress the activity of T-cells within and around transplanted organs. However, tacrolimus also suppresses T-cell function in the skin, contributing to a high incidence of skin cancer and associated mortality and morbidity in solid organ transplant recipients. Here, we aimed to identify a compound capable of re-establishing antitumor T-cell control in the skin despite the presence of tacrolimus. METHODS In this study, we performed time-resolved fluorescence resonance energy transfer to identify molecules capable of antagonizing the interaction between tacrolimus and FKBP12. The capacity of these molecules to rescue mouse and human T-cell function in the presence of tacrolimus was determined in vitro, and the antitumor effect of the lead compound, Q-2361, was assessed in "regressor" models of skin cancer in immunosuppressed mice. Systemic CD8 T-cell depletion and analyses of intratumoral T-cell activation markers and effector molecule production were performed to determine the mechanism of tumor rejection. Pharmacokinetic studies of topically applied Q-2361 were performed to assess skin and systemic drug exposure. RESULTS Q-2361 potently blocked the interaction between tacrolimus and FKBP12 and reversed the inhibition of the nuclear factor of activated T cells activation by tacrolimus following T-cell receptor engagement in human Jurkat cells. Q-2361 rescued T-cell function in the presence of tacrolimus, rapamycin, and everolimus. Intratumoral injection of Q-2361-induced tumor regression in mice systemically immune suppressed with tacrolimus. Mechanistically, Q-2361 treatment permitted T-cell activation, proliferation, and effector function within tumors. When CD8 T cells were depleted, Q-2361 could not induce tumor regression. A simple solution-based Q-2361 topical formulation achieved high and sustained residence in the skin with negligible drug in the blood. CONCLUSIONS Our findings demonstrate that the local application of Q-2361 permits T-cells to become activated driving tumor rejection in the presence of tacrolimus. The data presented here suggests that topically applied Q-2361 has great potential for the reactivation of T-cells in the skin but not systemically, and therefore represents a promising strategy to prevent or treat skin malignancies in immunosuppressed organ transplant recipients.
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Affiliation(s)
- Margaret Veitch
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Kimberly Beaumont
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, Queensland, Australia
| | - Rebecca Pouwer
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, Queensland, Australia
| | - Hui Yi Chew
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Ian H Frazer
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - H Peter Soyer
- Frazer Institute, Dermatology Research Centre, The University of Queensland, Brisbane, Queensland, Australia
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Scott Campbell
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Brian W Dymock
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, Queensland, Australia
| | - Andrew Harvey
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, Queensland, Australia
| | - Terrie-Anne Cock
- Queensland Emory Drug Discovery Initiative, UniQuest, The University of Queensland, Brisbane, Queensland, Australia
| | - James W Wells
- Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Frazer Institute, Dermatology Research Centre, The University of Queensland, Brisbane, Queensland, Australia
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Russomanno K, Abdel Azim S, Patel VA. Immunomodulators for Non-Melanoma Skin Cancers: Updated Perspectives. Clin Cosmet Investig Dermatol 2023; 16:1025-1045. [PMID: 37095898 PMCID: PMC10122480 DOI: 10.2147/ccid.s362171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 03/20/2023] [Indexed: 04/26/2023]
Abstract
Non-melanoma skin cancers (NMSCs) are the most common cancers worldwide and may be associated with significant morbidity and mortality, especially in immunosuppressed populations. Successful management of NMSC must take primary, secondary and tertiary prevention strategies into consideration. In response to an improved understanding of the pathophysiology of NMSC and associated risk factors, multiple systemic and topical immunomodulatory drugs have been developed and integrated into clinical practice. Many of these drugs are efficacious in the prevention and treatment of precursor lesions (actinic keratoses; AKs), low-risk NMSC, and advanced disease. The identification of patients at high risk for the development of NMSC is critical in reducing disease morbidity. Understanding the various treatment options available and their comparative effectiveness is paramount for developing a personalized treatment regimen for such patients. This review article provides an updated overview of the various topical and systemic immunomodulatory drugs available for the prevention and treatment of NMSC, and the published data supporting their use in clinical practice.
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Affiliation(s)
- Kristen Russomanno
- Department of Dermatology, Medstar Georgetown University Hospital/Medstar Medical Group, Washington, DC, USA
| | - Sara Abdel Azim
- School of Medicine, Georgetown University, Washington, DC, USA
| | - Vishal A Patel
- Department of Dermatology, George Washington University, Washington, DC, USA
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16
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Kreher MA, Noland MMB, Konda S, Longo MI, Valdes-Rodriguez R. Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids. J Am Acad Dermatol 2023; 88:521-530. [PMID: 36460257 DOI: 10.1016/j.jaad.2022.11.044] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/29/2022] [Accepted: 11/15/2022] [Indexed: 12/05/2022]
Abstract
Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.
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Affiliation(s)
| | | | - Sailesh Konda
- Department of Dermatology, University of Florida, Gainesville, Florida
| | - Maria I Longo
- Department of Dermatology, University of Florida, Gainesville, Florida
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17
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Zhang ZZ, Wen CH, Jia M, Zhang HQ, Sun SQ. Alkannin exerts antitumor properties in cutaneous squamous cell carcinoma by inducing apoptosis and shifting the M1/M2 polarization of tumor-associated macrophages by upregulating PTEN. Kaohsiung J Med Sci 2023; 39:70-79. [PMID: 36367154 DOI: 10.1002/kjm2.12617] [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: 05/11/2022] [Revised: 09/15/2022] [Accepted: 10/11/2022] [Indexed: 11/13/2022] Open
Abstract
Cutaneous squamous cell carcinoma (CSCC) is a common cancer in humans and is the second major type of skin cancer that causes death in humans. In this article, we investigated the effects of alkannin on CSCC progression. We revealed that alkannin curbed CSCC cell viability in a dose-dependent manner and accelerated CSCC cell apoptosis. In addition, alkannin expedited macrophage M1 polarization while curbing M2 polarization. Moreover, alkannin elevated phosphatase and tensin homolog (PTEN) abundance in CSCC cells. The results of bioinformatics analysis revealed that alkannin might modulate CSCC via PTEN. Downregulation of PTEN reversed the effects of alkannin on apoptosis of CSCC cells and M1/M2 polarization of macrophages. Alkannin reduced CSCC tumor growth in a mouse xenograft model. In conclusion, alkannin curbed the advancement of CSCC by expediting apoptosis and facilitating M1 polarization of macrophages by upregulating PTEN. These data may offer a therapeutic approach against CSCC.
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Affiliation(s)
- Zhong-Zhao Zhang
- Department of Dermatology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China
| | - Chang-Hui Wen
- Department of Dermatology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China
| | - Min Jia
- Department of Dermatology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China
| | - Hong-Qiang Zhang
- Department of Dermatology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China
| | - Shao-Qin Sun
- Department of Dermatology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China
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18
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Berman H, Shimshak S, Reimer D, Brigham T, Hedges MS, Degesys C, Tolaymat L. Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist. Mayo Clin Proc 2022; 97:2355-2368. [PMID: 36334939 DOI: 10.1016/j.mayocp.2022.07.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/29/2022] [Accepted: 07/07/2022] [Indexed: 11/06/2022]
Abstract
Solid organ transplant recipients (SOTRs) are at increased risk for the development of skin cancer compared with the general population, which requires consistent monitoring and management from a multidisciplinary team. The aim of this review is to provide a comprehensive overview for nondermatologist clinicians, outlining skin cancer diagnosis, treatment pearls, and skin cancer prevention strategies as they relate to SOTRs. A comprehensive search of the literature was conducted through the MEDLINE database with search terms including organ transplantation, transplant recipient, skin cancer, cutaneous neoplasms, management, and therapies. The search was limited to the English language and dates ranging from January 1, 2011, to December 28, 2021. All studies were reviewed for inclusion. Skin cancer will develop in more than half of SOTRs at some point in their life, most often nonmelanoma skin cancer such as basal cell carcinoma or squamous cell carcinoma. Melanoma and rarer cutaneous malignant neoplasms, such as Merkel cell carcinoma and Kaposi sarcoma, are also more frequent among SOTRs. A multidisciplinary effort at skin cancer screening and patient education is invaluable to prevent skin cancer-related morbidity and mortality in this population of patients. Reduction in immunosuppressive medications and surgical intervention are effective therapeutic approaches, and more novel systemic therapies including G protein-coupled receptor inhibitors and immune checkpoint inhibitors are possible options when traditional treatment approaches are not feasible. Checkpoint inhibitor therapy, however, comes with the risk of allograft rejection. With a growing and aging SOTR population, it is essential that SOTRs have support from dermatologists and nondermatologists alike in skin cancer prevention and treatment.
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Affiliation(s)
- Hannah Berman
- Department of Dermatology, Mayo Clinic, Jacksonville, FL
| | | | | | - Tara Brigham
- Mayo Clinic Medical Library, Mayo Clinic College of Medicine and Science, Jacksonville, FL
| | - Mary S Hedges
- Department of Internal Medicine, Division of Community Internal Medicine, Mayo Clinic, Jacksonville, FL
| | | | - Leila Tolaymat
- Department of Dermatology, Mayo Clinic, Jacksonville, FL.
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19
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Zheng YJ, Ho W, Sanlorenzo M, Vujic I, Daud A, Algazi A, Rappersberger K, Ortiz-Urda S. Melanoma risk during immunomodulating treatment. Melanoma Res 2022; 32:411-418. [PMID: 35993892 DOI: 10.1097/cmr.0000000000000838] [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: 10/15/2022]
Abstract
Immunosuppressive therapy is standard for the treatment of inflammatory diseases and for minimizing rejection in transplant patients. However, immunosuppressant drugs are associated with an increased risk of certain cancers. In particular, melanoma is an immunogenic tumor and as such, is strongly influenced by the immune system. We performed this literature review to summarize the effects of commonly used immunomodulating agents on melanoma development, recurrence and progression. We outline the mechanism of action of each drug and discuss the available evidence on its influence on melanoma. Based on existing literature, we recommend avoiding the following agents in patients with a history of invasive melanoma: cyclosporine, sirolimus, natalizumab, IL-6 inhibitors, cyclophosphamide, methotrexate and the tumor necrosis factor-alpha inhibitors infliximab and etanercept. If there are no viable alternative agents, we recommend for these patients to see a dermatologist every 6 months for a thorough skin examination.
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Affiliation(s)
- Yixuan James Zheng
- Department of Dermatology, University of California San Francisco
- School of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Wilson Ho
- Department of Dermatology, University of California San Francisco
| | - Martina Sanlorenzo
- Department of Dermatology, University of California San Francisco
- Department of Oncology, University of Turin, Torino, Italy
- Department of Medicine, Institute of Cancer Research, Medical University of Vienna
| | - Igor Vujic
- Department of Dermatology, University of California San Francisco
- Department of Dermatology and Venereology, The Rudolfstiftung Hospital
- School of Medicine, Sigmund Freud University Vienna, Vienna, Austria
| | - Adil Daud
- Department of Dermatology, University of California San Francisco
| | - Alain Algazi
- Department of Dermatology, University of California San Francisco
| | - Klemens Rappersberger
- Department of Dermatology and Venereology, The Rudolfstiftung Hospital
- School of Medicine, Sigmund Freud University Vienna, Vienna, Austria
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20
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Au EH, Wong G, Tong A, Teixeira-Pinto A, van Zwieten A, Dobrijevic E, Ahn C, Blosser CD, Davidson B, Francis A, Jhaveri KD, Malyszko J, Mena-Gutierrez A, Newell KA, Palmer S, Scholes-Robertson N, Silva Junior HT, Craig JC. Scope and Consistency of Cancer Outcomes Reported in Randomized Trials in Kidney Transplant Recipients. Kidney Int Rep 2022; 8:274-281. [PMID: 36815120 PMCID: PMC9939355 DOI: 10.1016/j.ekir.2022.10.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 11/11/2022] Open
Abstract
Introduction Cancer is an important outcome in kidney transplantation, but the scope and consistency of how cancer is defined and reported in trials involving kidney transplant recipients has not been evaluated. This study aimed to assess the range and variability of cancer outcomes in trials involving kidney transplant recipients. Methods The ClinicalTrials.gov database was searched from February 2000 to July 2021 to identify all randomized controlled trials (RCTs) in adult kidney transplant recipients, and which included cancer as a specified outcome. The definition of cancer, types of cancer (if any), timepoint(s) of measurement and method of aggregation were extracted for each cancer outcome. Results Of the 819 trials in kidney transplantation, only 84 (10%) included 1 or more cancer outcomes. Of these, 72 of 84 (86%) trials included cancer as a secondary outcome and 12 of 84 (14%) considered cancer as a primary outcome. The most frequent description of cancer was "malignancy" (n = 44, 43%), without reference to diagnostic criteria, histology, grade, or stage. The 2 most common cancer types were posttransplant lymphoproliferative disorder (PTLD) (n = 20, 20%) and nonmelanoma skin cancer (n = 10, 10%). Several methods of aggregation were identified, including incidence or rate (n = 47, 46%), frequency or proportion (n = 30, 29%), and time to event (n = 5, 5%). Approximately half the cancer outcomes were measured at a single time point (n = 44, 52%). Conclusion Cancer is an infrequently reported outcome and is inconsistently defined in trials of kidney transplant recipients. Consistent reporting of cancer outcomes using standardized definitions would provide important information on the impact of cancer in patients after kidney transplantation.
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Affiliation(s)
- Eric H. Au
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia,Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia,Correspondence: Eric H. Au, Center for Kidney Research, The Children’s Hospital at Westmead, Corner Hawkesbury Road and Hainsworth Street, Westmead, New South Wales 2145, Australia.
| | - Germaine Wong
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia,Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
| | - Allison Tong
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | - Anita van Zwieten
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | - Ellen Dobrijevic
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | - Curie Ahn
- Division of Nephrology, National Medical Center, Seoul, Korea
| | - Christopher D. Blosser
- Division of Nephrology, Department of Medicine, University of Washington School of Medicine, and Division of Nephrology, Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington, USA
| | - Bianca Davidson
- Division of Nephrology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Anna Francis
- Queensland Children's Hospital, Queensland, Australia
| | - Kenar D. Jhaveri
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, USA
| | - Jolanta Malyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | | | - Kenneth A. Newell
- Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Sarah Palmer
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | - Nicole Scholes-Robertson
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia,Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
| | | | - Jonathan C. Craig
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
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Chong S, Wong HY, Althabteh A, Cox C, Stevenson PH, Brown S, Griffin A, Isbel N, Siller G, Soyer HP, Schaider H, Roy E, Campbell S, Green AC, Khosrotehrani K. Chemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: A randomized, double-blind, placebo-controlled pilot trial. J Am Acad Dermatol 2022; 87:1163-1166. [PMID: 35219749 DOI: 10.1016/j.jaad.2022.02.039] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/02/2022] [Accepted: 02/15/2022] [Indexed: 10/31/2022]
Affiliation(s)
- Sharene Chong
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia
| | - Ho Yi Wong
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia
| | - Ahmad Althabteh
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia
| | - Charlotte Cox
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Paul H Stevenson
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Susan Brown
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia
| | - Anthony Griffin
- Department of Nephrology and Transplantation Services, Princess Alexandra Hospital, Brisbane, Australia
| | - Nicole Isbel
- Department of Nephrology and Transplantation Services, Princess Alexandra Hospital, Brisbane, Australia
| | - Gregory Siller
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia
| | - H Peter Soyer
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia; University of Queensland, UQ Diamantina Institute, Dermatology Research Centre, Brisbane, Australia
| | - Helmut Schaider
- Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia; University of Queensland, UQ Diamantina Institute, Dermatology Research Centre, Brisbane, Australia; Department of Dermatology, Sunshine Coast Hospital and Health Service, Birtinya, Queensland, Australia
| | - Edwige Roy
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia
| | - Scott Campbell
- Department of Nephrology and Transplantation Services, Princess Alexandra Hospital, Brisbane, Australia
| | - Adele C Green
- QIMR Berghofer Medical Research Institute, Brisbane, Australia; CRUK Manchester Institute and Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Kiarash Khosrotehrani
- University of Queensland, UQ Diamantina Institute, Experimental Dermatology Group, Brisbane, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Australia; University of Queensland, UQ Diamantina Institute, Dermatology Research Centre, Brisbane, Australia.
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22
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Sprangers B, Perazella MA, Lichtman SM, Rosner MH, Jhaveri KD. Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials. Kidney Int Rep 2022; 7:1939-1950. [PMID: 36090489 PMCID: PMC9458993 DOI: 10.1016/j.ekir.2022.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/10/2022] [Accepted: 06/06/2022] [Indexed: 11/06/2022] Open
Abstract
Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function. In subsequent preregistration studies, a limited number of patients with more severe kidney dysfunction are included. Data obtained from patients with either severe kidney dysfunction (here defined as an estimated glomerular filtration rate [eGFR] < 30 ml/min or stage 4G CKD) or end-stage kidney disease (ESKD) requiring kidney replacement treatment are particularly limited before drug registration and only a minority of new drug applications to the US Food and Drug Administration (FDA) include data from this population. Unfortunately, limited data and/or other safety concerns may result in a manufacturer statement that the drug is contraindicated in patients with advanced kidney disease, which hinders access to potentially beneficial drugs for these patients. This systemic exclusion of patients with CKD from cancer drug trials remains an unsolved problem, which prevents provision of optimal clinical care for these patients, raises questions of inclusion, diversity, and equity. In addition, with the aging of the population, there are increasing numbers of patients with CKD and cancer who face these issues. In this review, we evaluate the scientific basis to exclude patients with CKD from cancer trials and propose a comprehensive strategy to address this problem.
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Affiliation(s)
- Ben Sprangers
- Department of Microbiology and Immunology, Laboratory of Molecular Immunology, Rega Institute, KU Leuven, Leuven, Belgium
- Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Mark A. Perazella
- Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA
- Veterans Affairs Medical Center, West Haven, Connecticut, USA
| | - Stuart M. Lichtman
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Mitchell H. Rosner
- Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Kenar D. Jhaveri
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA
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23
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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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24
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Tong SH, Huang YJ, Yang YC, Lin HC, Jou YC. Hepatic Angiosarcoma Post-Renal Transplantation: A Case Report. Transplant Proc 2022; 54:1597-1600. [PMID: 35868873 DOI: 10.1016/j.transproceed.2022.05.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/05/2022] [Accepted: 05/21/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND DNA damage and oncogenic viruses increase the risk of cancer post-kidney transplantation, including skin cancer, Kaposi's sarcoma, oral cancer, and non-Hodgkin lymphoma. Here we report an uncommon case of liver angiosarcoma that occurred 8 years after kidney transplantation. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source. CASE REPORT A 57-year-old female patient received a cadaver kidney transplantation 8 years ago. She followed a long-term regimen of tacrolimus, mycophenolate sodium, and everolimus, with good renal function. She received annual regular abdominal ultrasound examinations after kidney transplantation, which showed no findings. The patient suffered from several symptoms for approximately 2 weeks before a scheduled abdominal ultrasound: diarrhea, epigastric pain, abdominal fullness, tea-colored urine, and little stool passage. The abdominal computerized tomography showed multiple hepatic tumors in both the hepatic lobes with engorged vasculatures and mild hemoperitoneum. A liver biopsy revealed the histopathology of angiosarcoma. The patient suffered multiple organ failure within one month of treatment. CONCLUSIONS Various post-transplant malignancies are not uncommon after transplantation, warranting periodic screenings for any symptoms in these patients.
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Affiliation(s)
- Show-Hwa Tong
- Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Yen-Ju Huang
- Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Yung-Cheng Yang
- Department of Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Hui-Chuan Lin
- Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Yeong-Chin Jou
- Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan; Division of Urology, Department of Surgery, St. Martin De Porres Hospital, Chia-Yi City, Taiwan.
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25
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Imamura R, Tanaka R, Taniguchi A, Nakazawa S, Kato T, Yamanaka K, Namba-Hamano T, Kakuta Y, Abe T, Tsutahara K, Takao T, Kishikawa H, Nonomura N. Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study. J Clin Med 2022; 11:249. [PMID: 35011990 PMCID: PMC8746009 DOI: 10.3390/jcm11010249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/27/2021] [Accepted: 12/29/2021] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.
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Affiliation(s)
- Ryoichi Imamura
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Ryo Tanaka
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Ayumu Taniguchi
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Shigeaki Nakazawa
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Taigo Kato
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Kazuaki Yamanaka
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Tomoko Namba-Hamano
- Department of Nephrology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;
| | - Yoichi Kakuta
- Osaka General Medical Center, Department of Urology, Osaka 558-8558, Japan; (Y.K.); (K.T.); (T.T.)
| | - Toyofumi Abe
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
| | - Koichi Tsutahara
- Osaka General Medical Center, Department of Urology, Osaka 558-8558, Japan; (Y.K.); (K.T.); (T.T.)
| | - Tetsuya Takao
- Osaka General Medical Center, Department of Urology, Osaka 558-8558, Japan; (Y.K.); (K.T.); (T.T.)
| | - Hidefumi Kishikawa
- Department of Urology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya 662-0918, Japan;
| | - Norio Nonomura
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; (R.T.); (A.T.); (S.N.); (T.K.); (K.Y.); (T.A.); (N.N.)
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26
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Colmenero J, Tabrizian P, Bhangui P, Pinato DJ, Rodríguez-Perálvarez ML, Sapisochin G, Bhoori S, Pascual S, Senzolo M, Al-Adra D, Herrero JI, Petrowsky H, Dawson LA, Hosni A, Kutzke JL, Gastaca M, Watt KD. De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference. Transplantation 2022; 106:e30-e45. [PMID: 34905760 DOI: 10.1097/tp.0000000000003998] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.
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Affiliation(s)
- Jordi Colmenero
- Liver Transplantation, Liver Unit Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | | | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi NCR, India
| | - David James Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Manuel L Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, University of Córdoba, IMIBIC, CIBERehd, Córdoba, Spain
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Toronto General Hospital, University of Toronto, ON, Canada
| | - Sherrie Bhoori
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Sonia Pascual
- Liver Unit, CIBERehd, ISABIAL, HGU Alicante, Alicante, Spain
| | - Marco Senzolo
- Multivisceral Transplant Unit, University Hospital of Padua, Padua, Italy
| | - David Al-Adra
- University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - J Ignacio Herrero
- Liver Unit, Clinica Universidad de Navarra, IdiSNA, CIBERehd, Pamplona, Spain
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Laura A Dawson
- Princess Margaret Cancer Centre/University Health Network, University of Toronto, Toronto, ON, Canada
| | - Ali Hosni
- Princess Margaret Cancer Centre/University Health Network, University of Toronto, Toronto, ON, Canada
| | | | - Mikel Gastaca
- Cruces University Hospital, Biocruces Bizkaia Health Research Institute, University of the Basque Country, Bilbao, Spain
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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27
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Robinson C, Chanchlani R, Kitchlu A. Malignancies after pediatric solid organ transplantation. Pediatr Nephrol 2021; 36:2279-2291. [PMID: 33057766 DOI: 10.1007/s00467-020-04790-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/28/2020] [Accepted: 09/18/2020] [Indexed: 12/19/2022]
Abstract
As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25-40 years). By 30 years following transplantation, 26-41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors.
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Affiliation(s)
- Cal Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- ICES McMaster, Hamilton, Ontario, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, 200 Elizabeth Street, 8 Eaton North, 8 N-842, Toronto, Ontario, M5G 2C4, Canada.
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28
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Reddy P, Yao M, Patel M. Investigative Landscape in Advanced Non-Melanoma Skin Cancers. Curr Treat Options Oncol 2021; 22:56. [PMID: 34097150 DOI: 10.1007/s11864-021-00853-0] [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] [Accepted: 03/31/2021] [Indexed: 01/21/2023]
Abstract
OPINION STATEMENT Advanced non-melanoma skin cancers have been challenging to treat due to limited treatment options. Treatment paradigm has shifted with the approval of immunotherapeutic agents cemiplimab and pembrolizumab which have been a key development and have changed the landscape of advanced or metastatic squamous cell skin cancers. Hedgehog inhibitors, vismodegib and sonidegib, remain upfront options for advanced or metastatic basal cell carcinomas. Current clinical trials are continuing to evaluate the use of immune checkpoint inhibitors and hedgehog pathway inhibitors. There is further need for ongoing research and development of new therapies in both malignancies.
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Affiliation(s)
- Priyanka Reddy
- Department of Hematology and Oncology, Department of Radiation Oncology, Case Comprehensive Cancer Center, 11100 Euclid Ave., Cleveland, OH, 44106, USA
| | - Min Yao
- Department of Radiation Oncology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, 11100 Euclid Ave., Cleveland, OH, 44106, USA
| | - Monaliben Patel
- Department of Oncology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
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29
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Murray SL, Daly FE, O'Kelly P, O'Leary E, Deady S, O'Neill JP, Dudley A, Rutledge NR, McCormick A, Houlihan DD, Williams Y, Morris PG, Ni Raghallaigh S, Moloney FJ, Sexton DJ, Conlon PJ. The impact of switching to mTOR inhibitor-based immunosuppression on long-term non-melanoma skin cancer incidence and renal function in kidney and liver transplant recipients. Ren Fail 2021; 42:607-612. [PMID: 32605413 PMCID: PMC7946013 DOI: 10.1080/0886022x.2020.1785499] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Solid organ transplantation is associated with increased risk of non-melanoma skin cancer. Studies with short follow up times have suggested a reduced occurrence of these cancers in recipients treated with mammalian target of rapamycin inhibitors as maintenance immunosuppression. We aimed to describe the occurrence of skin cancers in renal and liver transplant recipients switched from calcineurin inhibitor to sirolimus-based regimes. Methods We performed a retrospective study of sirolimus conversion within the Irish national kidney and liver transplant programs. These data were linked with the National Cancer Registry Ireland to determine the incidence of NMSC among these recipients. The incidence rate ratio (IRR) for post versus pre-conversion NMSC rates are referred in this study as an effect size with [95% confidence interval]. Results Of 4,536 kidney transplants and 574 liver transplants functioning on the 1 January 1994 or transplanted between 1 January 1994 and 01 January 1994 and 01 January 2015, 85 kidney and 88 liver transplant recipients were transitioned to sirolimus-based immunosuppression. In renal transplants, the rate of NMSC was 131 per 1000 patient years pre-switch to sirolimus, and 68 per 1000 patient years post switch, with adjusted effect size of 0.48 [0.31 − 0.74] (p = .001) following the switch. For liver transplant recipients, the rate of NMSC was 64 per 1,000 patient years pre-switch and 30 per 1,000 patient years post switch, with an adjusted effect size of 0.49 [0.22 − 1.09] (p .081). Kidney transplant recipients were followed up for a median 3.4 years. Liver transplants were followed for a median 6.6 years. Conclusions In this study, the conversion of maintenance immunosuppression from calcineurin inhibitors to mTOR inhibitors for clinical indications did appear to reduce the incidence of NMSC in kidney and liver transplant recipients.
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Affiliation(s)
- Susan L Murray
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland.,Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Fergus E Daly
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland
| | - Patrick O'Kelly
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland
| | - Eamonn O'Leary
- National Cancer Registry Ireland, Cork Airport Business Park, Cork, Ireland
| | - Sandra Deady
- National Cancer Registry Ireland, Cork Airport Business Park, Cork, Ireland
| | - James P O'Neill
- Department of Otolaryngology, Head & Neck Surgery, Beaumont Hospital, and Royal College of Surgeons, Ireland, Ireland
| | - Alexander Dudley
- Hepatology & Liver Transplant Department, St Vincent's University Hospital, Dublin, Ireland
| | - Nicholas R Rutledge
- Hepatology & Liver Transplant Department, St Vincent's University Hospital, Dublin, Ireland
| | - Aiden McCormick
- Hepatology & Liver Transplant Department, St Vincent's University Hospital, Dublin, Ireland
| | - Diarmuid D Houlihan
- Hepatology & Liver Transplant Department, St Vincent's University Hospital, Dublin, Ireland
| | - Yvonne Williams
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland
| | | | | | - Fergal J Moloney
- Department of Dermatology, Mater Misericordia University Hospital University College, Dublin, Ireland
| | - Donal J Sexton
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland
| | - Peter J Conlon
- Department of Nephrology & Transplantation, Beaumont Hospital, Dublin, Ireland.,Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
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30
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Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to Isoform-Specific Phosphoinositide 3-Kinase Inhibitors. Int J Mol Sci 2021; 22:ijms22073567. [PMID: 33808215 PMCID: PMC8036316 DOI: 10.3390/ijms22073567] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 03/19/2021] [Indexed: 12/20/2022] Open
Abstract
Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.
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31
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Cutaneous Head and Neck Cancers in the High-Risk Immunosuppressed Population. Otolaryngol Clin North Am 2021; 54:397-413. [PMID: 33602516 DOI: 10.1016/j.otc.2020.11.012] [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: 11/22/2022]
Abstract
The immunosuppressed (IS) population encompasses a diverse cohort of patients to include iatrogenically immunocompromised organ transplant recipients as well as patients with chronic lymphoid malignancies, human immunodeficiency virus/acquired immunodeficiency syndrome, and autoimmune disorders. Cutaneous cancers in this high-risk patient group are clinically distinct from the general immunocompetent population, showing aggressive behavior with associated poor outcomes. This article reviews the pathogenesis, epidemiology, incidence, prognosis, and special considerations required in managing cutaneous cancers in the IS patient population.
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32
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McMullen CP, Ow TJ. The Role of Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma. Otolaryngol Clin North Am 2021; 54:343-355. [PMID: 33583597 DOI: 10.1016/j.otc.2020.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Systemic therapy for patients with head and neck cutaneous squamous cell carcinoma (HNCSCC) generally is used for patients with advanced disease and most often employed for patients in the palliative setting when disease is unresectable and/or widely metastatic. Cytotoxic agents and epidermal growth factor receptor pathway targeted therapy have been utilized most commonly, with few clinical data to support their efficacy. Adjuvant postoperative chemoradiation with platinum has been called into question based on recent data. Programmed cell death protein 1 receptor immune checkpoint inhibitors have demonstrated profound activity in HNCSCC, and cemiplimab and pembrolizumab now are approved for use for unresectable/metastatic disease.
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Affiliation(s)
- Caitlin P McMullen
- Department of Head and Neck - Endocrine Oncology Program, Moffit Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
| | - Thomas J Ow
- Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, 3400 Bainbridge Avenue, 3rd Floor Medical Arts Pavilion, Bronx, NY 10467, USA; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, 3400 Bainbridge Avenue, 3rd Floor Medical Arts Pavilion, Bronx, NY 10467, USA
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33
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Préterre J, Visentin J, Saint Cricq M, Kaminski H, Del Bello A, Prezelin-Reydit M, Merville P, Kamar N, Couzi L. Comparison of two strategies based on mammalian target of rapamycin inhibitors in secondary prevention of non-melanoma skin cancer after kidney transplantation, a pilot study. Clin Transplant 2021; 35:e14207. [PMID: 33369772 DOI: 10.1111/ctr.14207] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 12/10/2020] [Accepted: 12/16/2020] [Indexed: 01/05/2023]
Abstract
After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.
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Affiliation(s)
- Julie Préterre
- CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, Bordeaux, France
| | - Jonathan Visentin
- CHU de Bordeaux, Service d'Immunologie et Immunogénétique, Hôpital Pellegrin, Bordeaux, France.,Université de Bordeaux, CNRS "ImmunoConcEpT" UMR 5164, Bordeaux, France
| | - Morgane Saint Cricq
- Department of Nephrology, Dialysis and Organ Transplantation, Hôpital Rangueil, CHU de Toulouse, Toulouse, France
| | - Hannah Kaminski
- CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, Bordeaux, France.,Université de Bordeaux, CNRS "ImmunoConcEpT" UMR 5164, Bordeaux, France
| | - Arnaud Del Bello
- Department of Nephrology, Dialysis and Organ Transplantation, Hôpital Rangueil, CHU de Toulouse, Toulouse, France.,Centre de Physiopathologie Toulouse Purpan, University Paul Sabatier, INSERM U1043, Toulouse, France
| | - Mathilde Prezelin-Reydit
- CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, Bordeaux, France
| | - Pierre Merville
- CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, Bordeaux, France.,Université de Bordeaux, CNRS "ImmunoConcEpT" UMR 5164, Bordeaux, France
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, Hôpital Rangueil, CHU de Toulouse, Toulouse, France.,Centre de Physiopathologie Toulouse Purpan, University Paul Sabatier, INSERM U1043, Toulouse, France
| | - Lionel Couzi
- CHU de Bordeaux, Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, Bordeaux, France.,Université de Bordeaux, CNRS "ImmunoConcEpT" UMR 5164, Bordeaux, France
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34
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Vecchiato M, Piaserico S, Biolo G, Frigo AC, Loy M, Rea F, Russo I, Alaibac M. Skin cancers in Italian lung transplant recipients: Incidence and risk factors analysis. Dermatol Ther 2021; 34:e14749. [PMID: 33403691 DOI: 10.1111/dth.14749] [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: 10/11/2020] [Revised: 12/24/2020] [Accepted: 12/30/2020] [Indexed: 11/29/2022]
Abstract
Only a few studies reported the incidence and risk factors of skin cancers in lung transplant recipients. The aim of this study was to determine the cumulative incidence of skin cancers in a cohort of patients undergoing lung transplantation and to define predictors of their development. About 247 consecutive patients receiving lung transplantation at the Thoracic Surgery Unit of University Hospital of Padova between May 1995 and October 2016 were studied. Cumulative incidence of skin cancers was estimated considering death as a competing event. The effect of potential predictors was evaluated with univariate and multivariable Cox models for competing risks. About 37 (15.0%) patients developed skin tumors. The cumulative incidence of any skin cancer was 14.2% at 5 years, 21.4% at 10 years, and 24.3% at 15 years posttransplantation. Age at transplantation, male gender, phototype II, and voriconazole use were independent risk factors for development of squamous cell carcinoma. Only male gender and phototype II were independent risk factors for development of basal cell carcinoma. Since lung transplant recipients have a greater risk of developing skin cancers, the management of these patients needs a multidisciplinary approach, in which dermatologists and transplant physicians have a primary role.
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Affiliation(s)
- Marco Vecchiato
- Sport and Exercise Medicine Division, Department of Medicine, University of Padova, Padova, Italy
| | - Stefano Piaserico
- Unit of Dermatology, Department of Medicine, University of Padova, Padova, Italy
| | - Giulia Biolo
- Unit of Dermatology, Department of Medicine, University of Padova, Padova, Italy
| | - Anna Chiara Frigo
- Biostatistics, Epidemiology, and Public Health Unit, Department of Cardiac, Thoracic, and Vascular Sciences, University Hospital, Padova, Italy
| | - Monica Loy
- Thoracic Surgical Unit, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy
| | - Federico Rea
- Thoracic Surgical Unit, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy
| | - Irene Russo
- Unit of Dermatology, Department of Medicine, University of Padova, Padova, Italy
| | - Mauro Alaibac
- Unit of Dermatology, Department of Medicine, University of Padova, Padova, Italy
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35
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Lim LM, Kung LF, Kuo MC, Huang AM, Kuo HT. Timing of mTORI usage and outcomes in kidney transplant recipients. Int J Med Sci 2021; 18:1179-1184. [PMID: 33526978 PMCID: PMC7847621 DOI: 10.7150/ijms.53655] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/18/2020] [Indexed: 12/17/2022] Open
Abstract
The introduction of mammalian target of rapamycin inhibitors (mTORi) as immunosuppressive agents has changed the landscape of calcineurin inhibitor-based immunosuppressive regimens. However, the timing of mTORi conversion and its associated outcomes in kidney transplantation have conflicting results. This study investigated the effect of early or late mTORi post-transplant initiation on major transplant outcomes, including post-transplant malignancy, in kidney transplant recipients in our center. We enrolled 201 kidney transplant recipients with surviving function grafts of >3 months between 1983 and 2016. Patients were divided into three groups: early mTORi (initiated within 6 months of kidney transplantation), late mTORi, (mTORi initiation >6 months after kidney transplantation) and no mTORi. The mean creatinine at conversion was 1.46 ± 0.48 mg/dL and 1.30 ± 0.53 mg/dL for the early and late mTORi groups, respectively. During the study period, 10.5% of mTORi users and 19.2% of mTORi nonusers developed malignancy, mainly urothelial carcinoma. After adjustment for confounding factors, mTORi users were found to have a lower incidence of post-transplant malignancy than did nonusers (adjusted OR: 0.28, P = 0.04). No significant difference was observed between early and late mTORi users. Our results verified the potential advantages of mTORi usage in reducing cancer incidence after kidney transplantation. However, no significant result was found related to the timing of mTORi introduction. Future studies should include a longer observation period with a larger cohort.
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Affiliation(s)
- Lee-Moay Lim
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Lan-Fang Kung
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Mei-Chuan Kuo
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - A-Mei Huang
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hung-Tien Kuo
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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36
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Naik MG, Arns W, Budde K, Diekmann F, Eitner F, Gwinner W, Heyne N, Jürgensen JS, Morath C, Riester U, Heller KM, Fischereder M. Sirolimus in renal transplant recipients with malignancies in Germany. Clin Kidney J 2020; 14:2047-2058. [PMID: 34476091 PMCID: PMC8406058 DOI: 10.1093/ckj/sfaa262] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 11/23/2020] [Indexed: 12/29/2022] Open
Abstract
Background Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Methods We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity. Results Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen’s disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with patients without a history of cancer. After conversion to SRL, cancer incidence rates (IRs) of all tumours were lower compared with rates before conversion. Cancer IRs after conversion were higher in patients with malignancy before conversion compared with those without. Patient survival was worse in patients with solid cancers compared with patients with skin cancers or without malignancies. Biopsy-proven acute rejections in the first year after conversion were less frequent in patients with malignancy compared with those without. Graft survival and renal function in all cancer types were better than in patients converted to SRL without cancers. Conclusions Conversion to SRL in patients with a history of cancer is safe regarding renal function and graft survival, while patient survival is largely dependent on tumour entity.
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Affiliation(s)
- Marcel G Naik
- Division of Nephrology, Charité University-Mitte, Berlin, Germany.,Berliner Institut für Gesundheitsforschung/Berlin Institute of Health (BIH) Körperschaft des öffentlichen Rechts Anna-Louisa-Karsch-Str. 2 10178 Berlinn, Germany
| | - Wolfgang Arns
- Transplant Centre Cologne, Cologne General Hospital, Cologne, Germany
| | - Klemens Budde
- Division of Nephrology, Charité University-Mitte, Berlin, Germany
| | - Fritz Diekmann
- Department of Nephrology and Kidney Transplantation, Hospital Clinic, Barcelona, Spain
| | - Frank Eitner
- Division of Nephrology and Immunology, Kidney Diseases Research, RWTH Aachen University Hospital, Bayer AG, Wuppertal, Germany
| | - Wilfried Gwinner
- Division of Nephrology, Hannover Medical School, Hannover, Germany
| | - Nils Heyne
- Division of Nephrology, University of Tübingen, Tübingen, Germany
| | | | - Christian Morath
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany
| | | | - Katharina M Heller
- Department of Medicine, Division of Nephrology, University of Erlangen, Erlangen, Germany
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37
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Stenz NA, Stampf S, Arnold AW, Cozzio A, Dickenmann M, Gaide O, Harms M, Hunger RE, Laffitte E, Mühlstädt M, Nägeli M, Hofbauer GFL. Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study). Dermatology 2020; 237:970-980. [PMID: 33227788 PMCID: PMC8619732 DOI: 10.1159/000510685] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 05/27/2020] [Indexed: 08/15/2023] Open
Abstract
IMPORTANCE Skin cancer, in particular squamous cell carcinoma, is the most frequent malignancy among solid organ transplant recipients with a higher incidence compared to the general population. OBJECTIVE To determine the skin cancer incidence in organ transplant recipients in Switzerland and to assess the impact of immunosuppressants and other risk factors. DESIGN Prospective cohort study of solid organ transplant recipients in Switzerland enrolled in the Swiss Transplant Cohort Study from 2008 to 2013. PARTICIPANTS 2,192 solid organ transplant recipients. MATERIALS AND METHODS Occurrence of first and subsequent squamous cell carcinoma, basal cell carcinoma, melanoma and other skin cancers after transplantation extracted from the Swiss Transplant Cohort Study database and validated by medical record review. Incidence rates were calculated for skin cancer overall and subgroups. The effect of risk factors on the occurrence of first skin cancer and recurrent skin cancer was calculated by the Cox proportional hazard model. RESULTS In 2,192 organ transplant recipients, 136 (6.2%) developed 335 cases of skin cancer during a median follow-up of 32.4 months, with squamous cell carcinoma as the most frequent one. 79.4% of skin cancer patients were male. Risk factors for first and recurrent skin cancer were age at transplantation, male sex, skin cancer before transplantation and previous transplantation. For a first skin cancer, the number of immunosuppressive drugs was a risk factor as well. CONCLUSIONS AND RELEVANCE Skin cancer following solid organ transplantation in Switzerland is greatly increased with risk factors: age at transplantation, male sex, skin cancer before transplantation, previous transplantation and number of immunosuppressive drugs.
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Affiliation(s)
- Nadja Angela Stenz
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Susanne Stampf
- Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland
| | - Andreas W Arnold
- Department of Dermatology, University Basel and Dermatologie am Rhein, Basel, Switzerland
| | - Antonio Cozzio
- Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Michael Dickenmann
- Division of Transplant Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Olivier Gaide
- Department of Dermatology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Mirjam Harms
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Robert E Hunger
- Department of Dermatology, Inselspital, University Hospital Berne, Berne, Switzerland
| | - Emmanuel Laffitte
- Division of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland
| | - Michael Mühlstädt
- Division of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland
| | - Mirjam Nägeli
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
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Interventions to Prevent Nonmelanoma Skin Cancers in Recipients of a Solid Organ Transplant: Systematic Review of Randomized Controlled Trials. Transplantation 2020; 103:1206-1215. [PMID: 31246934 DOI: 10.1097/tp.0000000000002641] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ transplant recipients are at high risk of developing skin cancer. The benefits and harms of interventions to prevent nonmelanoma skin cancer in solid organ transplant recipients have not been summarized. METHODS We searched MEDLINE, Embase, and CENTRAL through April 2018. Risk of bias was assessed using the Cochrane tool, and evidence certainty was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation process. Prespecified outcomes were nonmelanoma skin cancer, clearance and prevention of keratotic skin lesions, and intervention-specific adverse events. RESULTS Ninety-two trials (20 012 participants) were included. The evaluated treatments were cancer-specific interventions (acitretin, imiquimod, photodynamic therapy, nicotinamide, topical diclofenac, and selenium) and immunosuppression regimes (azathioprine, mycophenolate mofetil, calcineurin inhibitors, mammalian target of rapamycin [mTOR] inhibitors, belatacept, induction agents, and withdrawal of calcineurin inhibitors or corticosteroids). Effects on nonmelanoma skin cancer were uncertain for photodynamic therapy (3 trials, 93 participants, risk ratio [RR] 1.42 [95% confidence interval (CI), 0.65-3.11]; low certainty evidence), nicotinamide (2 trials, 60 participants), acitretin (2 trials, 61 participants), and imiquimod (1 trial, 20 participants) compared to control. mTOR inhibitors probably reduced skin cancer compared to calcineurin inhibitors (12 trials, 2225 participants, RR 0.62 [95% CI, 0.45-0.85]; moderate certainty evidence). Photodynamic therapy may cause pain at the treatment site (4 trials, 95 patients, RR 17.09 [95% CI, 4.22-69.26]; low certainty evidence). CONCLUSIONS There is limited evidence for the efficacy and safety of specific treatments to prevent nonmelanoma skin cancers among solid organ transplant recipients.
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James LJ, Saglimbene V, Wong G, Tong A, Luu LDW, Craig J, Howard K, Howell M. Behavioural and pharmaceutical interventions for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomised controlled trials. BMJ Open 2020; 10:e029265. [PMID: 32423925 PMCID: PMC7239542 DOI: 10.1136/bmjopen-2019-029265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients. We aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients. DESIGN Systematic review. DATA SOURCES We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019. ELIGIBILITY CRITERIA We included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients. DATA EXTRACTION AND SYNTHESIS Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework. RESULTS Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI -0.84 to 2.62, I2=98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I2 =72%) as the quality of evidence is very low. CONCLUSIONS Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice. PROSPERO REGISTRATION NUMBER CRD42017063962.
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Affiliation(s)
- Laura J James
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Valeria Saglimbene
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Germaine Wong
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, NSW, Australia
| | - Allison Tong
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Laurence Don Wai Luu
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Jonathan Craig
- College of Medicine and Public Health, Flinders University Faculty of Medicine Nursing and Health Sciences, Adelaide, South Australia, Australia
| | - Kirsten Howard
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
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Corchado-Cobos R, García-Sancha N, González-Sarmiento R, Pérez-Losada J, Cañueto J. Cutaneous Squamous Cell Carcinoma: From Biology to Therapy. Int J Mol Sci 2020; 21:ijms21082956. [PMID: 32331425 PMCID: PMC7216042 DOI: 10.3390/ijms21082956] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/18/2020] [Accepted: 04/20/2020] [Indexed: 12/13/2022] Open
Abstract
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.
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Affiliation(s)
- Roberto Corchado-Cobos
- Instituto de Biología Molecular y Celular del Cáncer (IBMCC)-Centro de Investigación del cáncer (CIC)-CSIC, Laboratory 7, 37007 Salamanca, Spain; (R.C.-C.); (N.G.-S.); (J.P.-L.)
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Complejo Asistencial Universitario de Salamanca, Hospital Virgen de la Vega, 37007 Salamanca, Spain;
| | - Natalia García-Sancha
- Instituto de Biología Molecular y Celular del Cáncer (IBMCC)-Centro de Investigación del cáncer (CIC)-CSIC, Laboratory 7, 37007 Salamanca, Spain; (R.C.-C.); (N.G.-S.); (J.P.-L.)
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Complejo Asistencial Universitario de Salamanca, Hospital Virgen de la Vega, 37007 Salamanca, Spain;
| | - Rogelio González-Sarmiento
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Complejo Asistencial Universitario de Salamanca, Hospital Virgen de la Vega, 37007 Salamanca, Spain;
- Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
| | - Jesús Pérez-Losada
- Instituto de Biología Molecular y Celular del Cáncer (IBMCC)-Centro de Investigación del cáncer (CIC)-CSIC, Laboratory 7, 37007 Salamanca, Spain; (R.C.-C.); (N.G.-S.); (J.P.-L.)
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Complejo Asistencial Universitario de Salamanca, Hospital Virgen de la Vega, 37007 Salamanca, Spain;
| | - Javier Cañueto
- Instituto de Biología Molecular y Celular del Cáncer (IBMCC)-Centro de Investigación del cáncer (CIC)-CSIC, Laboratory 7, 37007 Salamanca, Spain; (R.C.-C.); (N.G.-S.); (J.P.-L.)
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Complejo Asistencial Universitario de Salamanca, Hospital Virgen de la Vega, 37007 Salamanca, Spain;
- Department of Dermatology, Complejo Asistencial Universitario de Salamanca, 37007 Salamanca, Spain
- Correspondence: ; Tel.: +34-923-291-100 (ext. 55574)
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41
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Cheung CY, Tang SCW. An update on cancer after kidney transplantation. Nephrol Dial Transplant 2020; 34:914-920. [PMID: 30260424 DOI: 10.1093/ndt/gfy262] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Indexed: 12/31/2022] Open
Abstract
The emergence of onconephrology in recent years highlights the importance of the interaction between kidney disease and cancer. Chronic kidney disease (CKD) and cancer are linked with each other in different ways bidirectionally: cancer can cause CKD, whereas CKD itself may be a risk factor for cancer. Kidney transplant recipients (KTRs) have a 2- to 3-fold increased cancer risk when compared with the general population. The elevated risk covers a wide range of cancers. Some are related to CKD, including cancers of the kidney, urinary tract and thyroid, whereas others are related to oncogenic viruses that include non-Hodgkin lymphoma, cervical cancer, nonmelanoma skin cancer and Kaposi's sarcoma. There is no standard protocol regarding how immunosuppressive drugs should be adjusted in patients who develop posttransplant cancers. However, any modification of immunosuppressive regimens should be balanced against the risk of allograft rejection or deterioration in kidney function. Cancer surveillance can be used as a strategy to improve the clinical outcome in KTRs. Although guidelines adopted in the general population have been used as the reference, a personalized approach based on individual cancer risk, life expectancy and concurrent comorbidities has to be adopted.
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Affiliation(s)
- Chi Yuen Cheung
- Renal Unit, Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR
| | - Sydney Chi Wai Tang
- Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR
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Leiter U, Heppt MV, Steeb T, Amaral T, Bauer A, Becker JC, Breitbart E, Breuninger H, Diepgen T, Dirschka T, Eigentler T, Flaig M, Follmann M, Fritz K, Greinert R, Gutzmer R, Hillen U, Ihrler S, John SM, Kölbl O, Kraywinkel K, Löser C, Nashan D, Noor S, Nothacker M, Pfannenberg C, Salavastru C, Schmitz L, Stockfleth E, Szeimies R, Ulrich C, Welzel J, Wermker K, Garbe C, Berking C. S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) – short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow‐up, prevention and occupational disease. J Dtsch Dermatol Ges 2020; 18:400-413. [DOI: 10.1111/ddg.14072] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Ulrike Leiter
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Markus V. Heppt
- Department of Dermatology and AllergologyUniversity Medical Center LMU Munich Munich Germany
- Department of DermatologyFriedrich Alexander University of Erlangen‐Nuremberg Erlangen Germany
| | - Theresa Steeb
- Department of Dermatology and AllergologyUniversity Medical Center LMU Munich Munich Germany
- Department of DermatologyFriedrich Alexander University of Erlangen‐Nuremberg Erlangen Germany
| | - Teresa Amaral
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Andrea Bauer
- Department of DermatologyCarl Gustav Carus University Medical Center Dresden Germany
| | - Jürgen C. Becker
- Department of DermatologyEssen University Medical Center Essen Germany
| | | | - Helmut Breuninger
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Thomas Diepgen
- Institute for Clinical Social MedicineHeidelberg University Medical Center Heidelberg Germany
| | - Thomas Dirschka
- CentroDerm Clinic and Medical Faculty of Witten Herdecke University Wuppertal Germany
| | - Thomas Eigentler
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Michael Flaig
- Department of Dermatology and AllergologyUniversity Medical Center LMU Munich Munich Germany
| | | | | | | | - Ralf Gutzmer
- Department of Dermatology and AllergyHanover Medical School Hanover Germany
| | - Uwe Hillen
- Department of Dermatology and VenereologyVivantes Medical Center Berlin‐Neukölln Germany
| | | | - Swen Malte John
- Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm) at the University of Osnabrück Osnabrück Germany
| | - Oliver Kölbl
- Department of Radiation OncologyRegensburg University Medical Center Regensburg Germany
| | | | - Christoph Löser
- Department of DermatologyLudwigshafen Medical Center Ludwigshafen Germany
| | - Dorothee Nashan
- Department of DermatologyDortmund Medical Center Dortmund Germany
| | - Seema Noor
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Monika Nothacker
- Association of Scientific Medical Societies in Germany (AWMF) Berlin Germany
| | - Christina Pfannenberg
- Department of Diagnostic and Interventional RadiologyUniversity Medical Center Tübingen Germany
| | | | - Lutz Schmitz
- Department of DermatologyRuhr University of Bochum Bochum Germany
| | | | - Rolf‐Markus Szeimies
- Department of DermatologyKnappschaftskrankenhaus Recklinghausen Recklinghausen Germany
| | - Claas Ulrich
- Department of DermatologyCharité University Medical Center Berlin Germany
| | - Julia Welzel
- Department of Dermatology and AllergologyUniversity of Augsburg Augsburg Germany
| | - Kai Wermker
- Department of Oral and Maxillofacial SurgeryOsnabrück Medical Center Osnabrück Germany
| | - Claus Garbe
- Department of DermatologyEberhard Karls University of Tübingen Tübingen Germany
| | - Carola Berking
- Department of Dermatology and AllergologyUniversity Medical Center LMU Munich Munich Germany
- Department of DermatologyFriedrich Alexander University of Erlangen‐Nuremberg Erlangen Germany
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43
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Leiter U, Heppt MV, Steeb T, Amaral T, Bauer A, Becker JC, Breitbart E, Breuninger H, Diepgen T, Dirschka T, Eigentler T, Flaig M, Follmann M, Fritz K, Greinert R, Gutzmer R, Hillen U, Ihrler S, John SM, Kölbl O, Kraywinkel K, Löser C, Nashan D, Noor S, Nothacker M, Pfannenberg C, Salavastru C, Schmitz L, Stockfleth E, Szeimies RM, Ulrich C, Welzel J, Wermker K, Garbe C, Berking C. S3‐Leitlinie „Aktinische Keratose und Plattenepithelkarzinom der Haut“ – Kurzfassung, Teil 2: Epidemiologie, chirurgische und systemische Therapie des Plattenepithelkarzinoms, Nachsorge, Prävention und Berufskrankheit. J Dtsch Dermatol Ges 2020; 18:400-413. [PMID: 32291932 DOI: 10.1111/ddg.14072_g] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Ulrike Leiter
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Markus V Heppt
- Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians--Universität München, München.,Klinik für Dermatologie, Universitätsklinikum Erlangen
| | - Theresa Steeb
- Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians--Universität München, München
| | - Teresa Amaral
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Andrea Bauer
- Klinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Dresden
| | | | | | - Helmut Breuninger
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Thomas Diepgen
- Institut für klinische Sozialmedizin, Universität Heidelberg
| | | | - Thomas Eigentler
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Michael Flaig
- Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians--Universität München, München
| | | | | | | | - Ralf Gutzmer
- Klinik für Dermatologie, Medizinische Hochschule Hannover
| | - Uwe Hillen
- Klinik für Dermatologie, Vivantes Klinikum Neukölln, Berlin
| | | | - Swen Malte John
- Institut für interdisziplinäre Dermatologische Prävention und Rehabilitation (iDerm), Universität Osnabrück
| | - Oliver Kölbl
- Klinik für Strahlentherapie, Universitätsklinikum Regensburg
| | | | | | | | - Seema Noor
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF), Berlin
| | - Christina Pfannenberg
- Klinik für Diagnostische unter Interventionelle Radiologie, Eberhard-Karls-Universität Tübingen
| | | | - Lutz Schmitz
- Klinik für Dermatologie, Ruhr-Universität Bochum
| | | | | | - Claas Ulrich
- Klinik für Dermatologie, Charité - Universitätsmedizin Berlin
| | | | - Kai Wermker
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Klinikum Osnabrück
| | - Claus Garbe
- Klinik für Dermatologie, Eberhard-Karls-Universität Tübingen, Tübingen
| | - Carola Berking
- Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians--Universität München, München.,Klinik für Dermatologie, Universitätsklinikum Erlangen
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European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer 2020; 128:60-82. [PMID: 32113941 DOI: 10.1016/j.ejca.2020.01.007] [Citation(s) in RCA: 140] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 01/15/2020] [Indexed: 12/19/2022]
Abstract
Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women's Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography-computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.
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Plasmeijer E, Sachse M, Gebhardt C, Geusau A, Bouwes Bavinck J. Cutaneous squamous cell carcinoma (cSCC) and immunosurveillance – the impact of immunosuppression on frequency of cSCC. J Eur Acad Dermatol Venereol 2019; 33 Suppl 8:33-37. [DOI: 10.1111/jdv.16025] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 10/21/2019] [Indexed: 12/22/2022]
Affiliation(s)
- E.I. Plasmeijer
- Department of Dermatology Erasmus Medical Centre Rotterdam The Netherlands
| | - M.M. Sachse
- Department of Dermatology, Allergy and Phlebology Hospital of Bremerhaven Bremerhaven Germany
| | - C. Gebhardt
- Department of Dermatology and Venerology University Hospital Hamburg‐Eppendorf (UKE) Hamburg Germany
| | - A. Geusau
- Department of Dermatology Medical University of Vienna Vienna Austria
| | - J.N. Bouwes Bavinck
- Department of Dermatology Leiden University Medical Centre Leiden The Netherlands
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Evolving Role of Systemic Therapies in Non-melanoma Skin Cancer. Clin Oncol (R Coll Radiol) 2019; 31:759-768. [PMID: 31522944 DOI: 10.1016/j.clon.2019.08.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 08/16/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023]
Abstract
Keratinocyte cancers - basal and cutaneous squamous cell carcinoma (BCC, cSCC) - are the most common forms of non-melanoma skin cancer (NMSC) and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. In these clinical circumstances, systemic treatment may be indicated, and over the past 10 years a number of new systemic agents have been approved. Nonetheless, effective systemic therapy for keratinocyte cancers remains an area of significant unmet clinical need. Improved understanding of the molecular and immune pathogenesis underlying tumour growth and development is critical for driving future advances and is a research priority. The aim of this review is to provide clinicians with an overview of systemic treatments for BCC and cSCC and will focus on current evidence for conventional chemotherapy, targeted therapies, immunotherapy, adjuvant and neoadjuvant therapy, chemoprevention and future prospects for novel systemic treatment approaches.
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47
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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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48
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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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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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50
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Gender, Race and Disease Etiology Predict De Novo Malignancy Risk After Liver Transplantation: Insights for Future Individualized Cancer Screening Guidance. Transplantation 2019; 103:91-100. [PMID: 29377876 DOI: 10.1097/tp.0000000000002113] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database. METHODS The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy. RESULTS Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS). CONCLUSIONS This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.
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