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肝细胞癌肝移植受者的免疫抑制策略

Strategies of immunosuppression for liver transplant recipients with hepatocellular carcinoma.

作者信息

Castroagudín J F, Molina-Pérez E, Ferreiro-Iglesias R, Varo-Pérez E

机构信息

University Hospital of Santiago, Santiago de Compostela, Spain.

出版信息

Transplant Proc. 2011 Apr;43(3):711-3. doi: 10.1016/j.transproceed.2011.01.090.

Abstract

Liver transplantation is considered to be the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rate. The application of restrictive selection criteria based on tumor size and number of nodules is advised to obtain optimal results. Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pretransplant staging and patient selection. Post transplant recurrence of hepatocarcinoma clearly has a major negative impact on prognosis. Intuitively, an immunosupressed state is undesirable in cancer patients. Inversely, modulation or minimization of immunosuppressive therapy could influence tumor progression and reduce the negative impact of recurrence on posttransplant survival. Experimental evidence shows that mammalian target of rapamycin (mTOR) inhibitors have antiangiogenic and antiproliferative effects. Thus, their application has been proposed as antineoplastic agents for immunosuppressive protocols in liver transplant recipients with HCC and may reduce the rate or the impact of tumor recurrence. Clinical data about efficacy and safety of mTOR-based immunosuppressant protocols in liver transplant recipients with HCC show promising results, namely low recurrence and higher survival rates compared with standard calcineurin inhibitor-based immunosuppressive protocols, even among patients with extended morphological criteria. The safety profile is regarded generally as adequate.

摘要

就总体生存率和复发率而言,肝移植被认为是肝硬化和早期肝细胞癌(HCC)患者最有效的治疗选择。建议应用基于肿瘤大小和结节数量的限制性选择标准以获得最佳效果。然而,尽管进行了仔细的移植前分期和患者选择,仍有3.5%至21%的受者会发生肿瘤复发。肝癌移植后复发显然对预后有重大负面影响。直观地说,免疫抑制状态对癌症患者是不利的。相反,免疫抑制治疗的调节或最小化可能会影响肿瘤进展,并减少复发对移植后生存的负面影响。实验证据表明,雷帕霉素靶蛋白(mTOR)抑制剂具有抗血管生成和抗增殖作用。因此,已提议将其作为抗瘤药物应用于患有HCC的肝移植受者的免疫抑制方案中,并可能降低肿瘤复发率或影响。关于基于mTOR的免疫抑制方案在患有HCC的肝移植受者中的疗效和安全性的临床数据显示出有前景的结果,即与基于标准钙调神经磷酸酶抑制剂的免疫抑制方案相比,复发率低且生存率更高,即使在具有扩展形态学标准的患者中也是如此。其安全性概况总体上被认为是足够的。

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