Retrospective studies have demonstrated that patients who are expressors of cytochrome P4503A5 (CYP3A5) require a higher tacrolimus dose to achieve a therapeutic trough concentration (C(0)). The aim of this study was to evaluate this effect prospectively by pretransplantation adaptation. We randomly assigned 280 renal transplant recipients to receive tacrolimus either according to CYP3A5 genotype or according to the standard daily regimen. The primary end point was the proportion of patients within the targeted C(0). Secondary end points included the number of dose modifications and the delay in achieving the targeted C(0). In the group receiving the adapted dose, a higher proportion of patients had values within the targeted C(0) at day 3 after initiation of tacrolimus (43.2% vs. 29.1%; P = 0.03); they required fewer dose modifications, and the targeted C(0) was achieved by 75% of these patients more rapidly. The clinical end points were similar in the two groups. Pharmacogenetic adaptation of the daily dose of tacrolimus is associated with improved achievement of the target C(0). Whether this improvement will affect clinical outcomes requires further evaluation.
Purpose: To review the available options of percutaneous ablation of lung metastasis. Methods: General indications, prognostic factors, and image guidance of percutaneous lung ablations were reviewed. Specificities, technical aspects, advantages and limitations of each technic were highlighted. Complications and follow up where also reviewed. Results: Image-guided, percutaneous ablation is of interest for patients with a limit number (<3-5) small metastases (<2-3 cm). Other predictive factors have been reported such as the disease-free interval, the primary tumor, or the proximity with large vessels or bronchus. Radiofrequency ablation (RFA) is the most reported technic, with local control rate >90% for small tumors, and a very low complication rate. Microwave (MWA) and cryoablation are alternative technics developed in the last 15 years to overcome RFA limitations, with encouraging results. Larger ablations zones and less heat sink effect have been described with MWA. On the other hand, cryoablation allows painless treatments under conscious sedation and/or local anesthesia, high accessibility of difficult locations and promising results on prospective multicenter series. Although irreversible electroporation (IRE) could be used for lesions close to main blood vessels as it is not limited by the heat sink effect and does not have significant effects on connective tissue, allowing to treat lesions near to vital organs, preliminary results for lung metastasis are disappointing. Conclusion: Percutaneous ablation of lung metastases, whatever technic is used, is feasible, with high local control rate, and acceptable complication rate. Although indications seem clear enough, validation through controlled trials is mandatory.
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