巴塞罗那学者研究发现雷帕霉素能显著降低肾移植病人罹患癌症的风险

2009年2月20日 20:26 肾友网   肾友网阅读:211次
 

  肾友网译自外电 本月出版的美国肾脏学会杂志发表的一项研究报告显示,肾移植手术三个月以后用雷帕霉素替代环孢霉素治疗的病人罹患癌症的比率降低了超过50%.

新闻链接:癌症,伴随器官移植而来? 2003/9/18

成功大学医学院附设医院外科主治医师 陈明镇

  年近七十的詹先生除了慢性肾衰竭而接受规则洗肾四年外,身体还算硬朗并无其它的重大疾病。在朋友与家人的劝说下,终于鼓起勇气到中国大陆接受肾脏移植,本以为幸福的日子就此来临,不料恶梦随之而来。就在移植后的三个月,詹先生因为突发性急性腹痛被送至本院,经过一系列检查,却发现詹先生竟然已经是癌症末期,在腹腔内、颈部淋巴腺、骨头其至大脑中都存有转移的腺癌细胞,不到一个月的时间(距离接受肾脏移植不到五个月)詹先生便离开人世。

  "癌症,伴随器官移植而来?"似乎是个耸动的标题,但有上述案例的印证,它却是事实。与器官移植相关的恶性肿瘤,大致有两种形成机制。第一种是原先存在于捐赠者身上,经由移植的手术过程被带入至受赠者身上,经由对捐赠者适当的筛选,此种和捐赠者相关的恶性肿瘤是可以避免的。另一种移植后癌症发生机制则更普遍,也更难以预防,所有移植患者术后都要长期服用免疫抑制剂来使体内免疫力降低,以防止器官排斥的情况发生,而长期服用免疫抑制剂的副作用,一是感染,另一则是恶性肿瘤的产生。

  移植后自身所长出之癌症也有特定性。例如:皮肤癌的发生机率最高,约为正常人的一百倍;另外像淋巴癌、肝癌、会阴部及泌尿道癌症发生之机率也比正常人高出数十倍之多。综合来说,移植后自身所长出的癌症发生率从4%到40%不等,世界各国的统计不一,这和每家医院采用的免疫抑制剂剂量有密切相关,所用的免疫抑制剂剂量愈强,将来病人得到恶性肿瘤的机会就愈高。成大医院自从1990年完成第一例肾脏移植后至今,目前的移植物存活机率并不逊色于欧美国家,而移植后癌症发生率为5%,则低于世界各国的报导数据,主要的原因是本院所使用的免疫抑制剂剂量较国外低。如此一来,不仅用药成本下降,病人感染与癌症风险下降,而且所移植的器官并未因此而容易发生排斥的现象。

  传统的免疫抑制剂(例如: 环孢灵…)使人的免疫力降低,因而有致癌的风险,而依据"自然医学"杂志最近的报导,新的免疫抑制剂-斥消灵(sirolimus)却有抑制肿瘤生长之效用。本院于2001年即开始用此新药,并致力观察与研究其抑制肿瘤生长之功效。有此新药做为武器,加上良好运用传统免疫抑制剂的艺术,相信能为移植患者提供一安全、信赖的用药哲学。

附英文新闻稿及研究详细情况介绍:

Sirolimus Reduces the Risk of Cancer in Kidney Transplant Patients

Thursday February 9, 11:41 am ET

BERLIN, Feb. 9 /PRNewswire/  A new study published in this month's issue of the Journal of the American Society of Nephrology shows that the risk of cancer in kidney transplant recipients was reduced by more than 50% at five years post transplantation in those patients who were treated with sirolimus following withdrawal of cyclosporine at three months.

Cancer is now the second most common cause of premature death in kidney transplant recipients with an incidence of up to 10 times that seen in the general population. To date this risk has largely been considered to be due to overall immunosuppression as a class effect of the drugs used.

"Post transplant malignancies are a major cause of morbidity and death associated with maintenance immunosuppression following organ transplantation," said Dr Josep Campistol, Director of the Clinical Institute of Nephrology and Urology, of the Hospital Clinic de Barcelona. "The findings of this study are enormously important for transplant patients, not least because cancer is the second most common cause of premature death in these patients."

He continued: "Notably this study demonstrates that sirolimus can delay the appearance and/or decrease the frequency of malignancy in these patients. Longer follow up and additional trials are therefore needed to confirm what are already promising results."

Details of the study

In this analysis of the Rapamune Maintenance Study, 430 kidney transplant patients were randomly assigned to remain on sirolimus (SRL), cyclosporine (CsA) and steroids (ST) or to have cyclosporine withdrawn.

Skin carcinoma

Any skin cancer also included melanoma, Bowen's disease, and non-specified skin cancers.

Intention-to-treat (ITT) analyses of any skin carcinoma are given below:

* At 5 years, with regard to any skin carcinoma there were fewer lesions

with cyclosporine withdrawal, 109 vs 39 (SRL-CsA-ST vs SRL-ST), and the

mean annualized rates were lower, 107.7 vs 35.8 (SRL-CsA-ST vs SRL-ST).

* The time to development of first skin carcinoma was delayed with

cyclosporine withdrawal (median time to first skin carcinoma was 491 vs

1126 days; P = 0.007).

* The relative risk of any skin carcinoma was 65% lower in those patients

in whom cyclosporine was withdrawn (relative risk SRL-ST to SRL-CsA-ST

0.346; 95% confidence interval 0.227 to 0.556; P < 0.001).

* The relative risk of both of the most common forms of skin carcinoma

(basal cell and squamous cell carcinomas) were significantly lower with

SRL+ST.

Non-skin cancers

Non-skin cancers observed in the study were: lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid and cervix as well as glioma, lipsosarcoma, astrocytoma, leukaemia, lymphoma and Kaposis's Sarcoma.

The number of non-skin malignancies recorded in the patients maintained on cyclosporine was 18 compared with only 8 in the group who had cyclosporine withdrawn. Non-skin malignancy-free survival rate was higher with cyclosporine withdrawal, 90.38% vs 95.99% (SRL-CsA-ST vs SRL-ST). P = 0.032, ITT analysis.

Offering kidney transplant recipients a sirolimus-based therapy may give patients an opportunity to reduce their risk of developing cancer after a successful kidney transplant.

This analysis is one of a series of data reviews conducted of the Rapamune Maintenance Regimen study.

Source: Hospital Clinic de Barcelona


稍新:肾功能不佳患者 别吃高钾食物
早前:黄芪注射液可改善腹膜透析的疗效