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A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation.

ABSTRACT: Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS regimen following diagnosis and the oncological treatment approach were analyzed: Kaplan−Meier analysis as well as univariate and multivariate analysis were performed. Results: A total of 33 out of 2744 patients were diagnosed with CRC after LT. Two groups were identified: patients with restrictive IS management undergoing dose reduction (RIM group, n = 20) and those with unaltered regimen (maintenance group, n = 13). The groups did not differ in clinical and oncological characteristics. Statistically significant improved survival was found in Kaplan−Meier analysis for patients in the RIM group with 83.46 (8.4−193.1) months in RIM and 24.8 (0.5−298.9) months in the maintenance group (log rank = 0.02) and showed a trend in multivariate cox regression (p = 0.054, HR = 14.3, CI = 0.96−213.67). Conclusions: Immunosuppressive therapy should be reduced further in patients suffering from CRC after LT in an individualized manner to enable optimal oncological therapy and enable improved survival.

SUBMITTER: Ossami Saidy RR

PROVIDER: S-EPMC9785597 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation.

Ossami Saidy Ramin Raul RR Wegener Elisa E Uluk Deniz D Dittrich Luca L Schöning Wenzel W Lurje Georg G Öllinger Robert R Modest Dominik Paul DP Tacke Frank F Haase Oliver O Pratschke Johann J Eurich Dennis D

Medicina (Kaunas, Lithuania) 20221129 12

Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS reg ...[more]

PMID: 36556957

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Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.

Project description:BackgroundLiver transplant (LT) recipients, particularly children, have an increased risk of developing de novo food allergies (FAs) after transplantation both compared to all the other transplant groups and to the general population. Little is known about the pathogenesis underlying this phenomenon and comprehensive recommendations or clinical practice guidelines are still lacking, mainly due to the scarcity of high-quality evidence.AimWe aimed to prepare a systematic review on de novo FA in pediatric LT recipients to assess epidemiology and risk factors, evaluate the correlation to specific food groups, describe clinical manifestations, investigate the rate of tolerance acquisition over time and report available therapeutic strategies.MethodsWe conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, Scopus, Web of Science, Wiley online library, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for studies published from January 1980 to September 2021. All the articles were checked independently by two reviewers in two steps. A total of 323 articles were screened, and 40 were included for data extraction.Results and conclusionsWe found that de novo FAs develop in the 15% of pediatric LT recipients, especially in the first 2 years after surgery, with higher risk related to younger age at transplantation (especially <2 years of age) and tacrolimus immunosuppression. Subjects are often allergic to multiple foods, and 15% of them suffer from anaphylaxis. The majority of patients do not spontaneously outgrow their symptoms during follow-up. The discontinuation of tacrolimus in favor of cyclosporine or the association of tacrolimus with mycophenolate have been associated with the resolution or the improvement of FA in small retrospective case series and could be considered in case of severe or multiple, difficult to manage FAs. Prospective multicenter studies are needed to confirm these findings, guide the risk-based stratification of pediatric LT recipients, and provide for high-evidence therapeutic strategies for children with de novo FA.

Project description:AimsInvasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise.Methods and resultsNinety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7-11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7-11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics.ConclusionsDe novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.

Dataset Information

A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation.

Publications

A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation.

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