探讨肝移植术后新发恶性肿瘤的危险因素和防治措施。

回顾性研究2003年10月至2008年12月在中山大学附属第三医院肝移植中心行肝移植且接受完整随访的416例中9例新发恶性肿瘤患者临床资料。其中男7例，女2例；年龄30～60岁，中位年龄57岁。术前有吸烟史4例、长期二手烟接触史3例，1例有肝细胞癌（肝癌）家族史。所有患者均签署知情同意书，符合医学伦理学规定。肝移植手术方式均为同种异体改良背驮式肝移植术，采用甲泼尼龙+他克莫司（FK506）或环孢素（CsA）免疫抑制方案。患者术后接受随访，观察新发恶性肿瘤的发生、治疗、预后等情况。

肝移植术后新发恶性肿瘤发生率为2.2%（9/416），其中消化系统恶性肿瘤3例、呼吸系统恶性肿瘤3例、血液系统恶性肿瘤2例、软组织肉瘤1例。肝移植至肿瘤确诊的时间为10～73个月，中位时间49个月。患者接受相应的手术治疗、放射治疗（放疗）、化学药物治疗（化疗）。5例术后免疫抑制剂转换为西罗莫司，4例FK506用量为肿瘤确诊前的半量。随访期间6例死亡，均死于肿瘤进展和多器官功能衰竭。确诊距死亡的时间为2～25个月，中位时间9个月。

吸烟和免疫抑制剂的应用可能为肝移植术后新发恶性肿瘤发生的高危因素，进行规范化随访并针对高危因素早期防治是提高疗效的关键。

To investigate the risk factors, prophylaxis and treatment of de novo malignancies following liver transplantation (LT).

Clinical data of 9 patients with de novo malignancies out of 416 patients who underwent LT and received complete follow-up in Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to December 2008 were analyzed retrospectively. Seven patients were male and 2 were female. The age ranged from 30 to 60 years old with a median of 57 years old. Four cases had smoking history before operation, 3 cases had long-term passive smoke exposure, and 1 case had family history of hepatocellular carcinoma. The informed consents of all patients were obtained and the ethical committee approval was received. Allogeneic modified piggyback LT was performed in all the patients. The immunosuppressive regimen was methylprednisolone + tacrolimus (FK506) or cyclosporine A (CsA). The patients were followed up after operation and the incidence, treatments and prognosis of de novo malignancies were observed.

The incidence of de novo malignancies following LT was 2.2% (9/416) including digestive system malignancies (n=3), respiratory system malignancies (n=3), hematological malignancies (n=2) and soft tissue sarcoma (n=1). The elapsed time from LT to diagnosis was 10 to 73 months (median: 49 months). The patients received surgery, radiotherapy, chemotherapy accordingly. After the operation, the immunosuppressant of 5 patients changed to sirolimus and 4 patients continued to take FK506 half the dose before tumor diagnosis. Six cases died of tumor progress and multiple organ failure during the follow-up. The interval time from diagnosis of tumor to death ranged from 2 to 25 months (median: 9 months).

Smoking and use of immunosuppressant may be high risk factors of de novo malignancy following liver transplantation. Normative follow-up and prophylaxis and treatment at the earlier stage are the keys to improve the therapeutic effect.