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De Novo Carcinoma after Solid Organ Transplantation to Give Insight into Carcinogenesis in General-A Systematic Review and Meta-Analysis.

ABSTRACT: Immunosuppressive therapy after solid organ transplantation leads to the development of cancer in many recipients. Analysis of the occurrence of different types of de novo carcinomas in relation to specific immunosuppressive drugs may give insight into their carcinogenic process and carcinogenesis in general. Therefore, a systematic search was performed in Embase and PubMed. Studies describing over five de novo carcinomas in patients using immunosuppressive drugs after solid organ transplantation were included. Incidence per 1000 person-years was calculated with DerSimonian-Laird random effects model and odds ratio for developing carcinomas with the Mantel-Haenszel test. Following review of 5606 papers by title and abstract, a meta-analysis was conducted of 82 studies. The incidence rate of de novo carcinomas was 8.41. Patients receiving cyclosporine developed more de novo carcinomas compared to tacrolimus (OR1.56, 95%CI 1.00-2.44) and mycophenolate (OR1.26, 95%CI 1.03-1.56). Patients receiving azathioprine had higher odds to develop de novo carcinomas compared to mycophenolate (OR3.34, 95%CI 1.29-8.65) and head and neck carcinoma compared to tacrolimus (OR3.78, 95%CI 1.11-12.83). To conclude, patients receiving immunosuppressive drugs after solid organ transplantation have almost a 20-fold increased likelihood of developing carcinomas, with the highest likelihood for patients receiving cyclosporine A and azathioprine. Looking into altered immune pathways affected by immunosuppressive drugs might lead to better understanding of carcinogenesis in general.

SUBMITTER: Zwart ES

PROVIDER: S-EPMC7961956 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposePosterior reversible encephalopathy syndrome (PRES) is known to occur after solid organ transplantation (SOT), potentially associated with cyclosporine and tacrolimus. In this study, we assess the frequency and clinical and imaging characteristics of PRES after SOT.Materials and methodsWe identified 27 patients (13 men and 14 women; age range, 22-72 years) who developed PRES after SOT. Features noted included SOT subtype, incidence and timing of PRES, infection and rejection, mean arterial pressure (MAP), and toxicity brain edema.ResultsPRES developed in 21 (0.49%) of 4222 patients who underwent transplantation within the study period (no significant difference among SOT subtypes). Transplantation was performed in 5 patients before the study period, and 1 patient underwent transplantation elsewhere. In consideration of all 27 patients, PRES typically developed in the first 2 months in patients who had SOT of the liver (9 of 10 patients) and was associated with cytomegalovirus (CMV), mild rejection, or systemic bacterial infection. PRES also typically developed after 1 year in patients who had SOT of the kidney (8 of 9 patients) and was associated with moderate rejection or bacterial infection. Toxicity MAP was significantly lower (P < .001) in liver transplants (average MAP, 104.8 +/- 16 mm Hg) compared with that in kidney transplants (average MAP, 143 +/- 20 mm Hg). Toxicity brain edema was significantly greater (P < .001) in patients who had liver transplants and developed PRES compared with patients who had undergone kidney transplants despite severe hypertension in those who had the kidney transplants.ConclusionPatients who had undergone SOTs have a similar low incidence of developing PRES. Differences between those who have had liver and kidney transplants included time after transplant, toxicity MAP, and PRES vasogenic edema noted at presentation. In patients who have undergone kidney transplants, severely elevated MAP was associated with reduced, not greater, brain edema.

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De Novo Carcinoma after Solid Organ Transplantation to Give Insight into Carcinogenesis in General-A Systematic Review and Meta-Analysis.

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