Mammalian target of rapamycin (mTOR) inhibitors slow skin carcinogenesis, but impair wound healing
Mammalian target of rapamycin (mTOR) inhibitors slow skin carcinogenesis, but impair wound healing
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DOI：
10.1111/j.1365-2133.2011.10591.x
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发表时间：
2012-02-01
影响因子：
10.3
通讯作者：
Hafner, J.
中科院分区：
文献类型：
--
作者：
Feldmeyer, L.;Hofbauer, G. F. L.;Hafner, J.
背景：最近的研究表明，与钙调神经磷酸酶抑制剂相比，服用哺乳动物靶向雷帕霉素(MTOR)抑制剂的患者皮肤癌的发生率估计减少了50%或更多。在随机试验进行期间，当皮肤癌变增加时，器官移植受者经常从钙调神经磷酸酶抑制剂转换为mTOR抑制剂。目的为了减缓心脏移植受者的癌变，该患者患有神经病理性糖尿病足综合征，每年发生皮肤癌的比率超过20例。方法将患者的免疫抑制从钙调神经磷酸酶抑制剂环孢菌素改为mTOR抑制剂维拉莫司。结果每年的癌变速度减慢至6例；然而，他出现了顽固性糖尿病足溃疡，这是纯粹的神经病变和非血管病变，以及威胁右腿瘘管的坏死性骨盆。这两个网站对抗生素治疗、卸货和清创的反应都很差。这种皮瘘变成了慢性的，一些脚趾有轻微截肢的风险。鉴于mTOR抑制剂有损害Will愈合的倾向，免疫抑制被重新转换为环孢素。所有创面均迅速愈合，但皮肤癌的发生率上升到以前的水平。结论这一病例深刻地说明了mTOR抑制剂在临床上的两难境地，即在致癌方面的好处与在伤口愈合方面的损害相抵消。因此，免疫抑制方案的改变应该在个人的基础上进行，并仔细考虑相关的风险。
Background Recent studies suggest that patients on mammalian target of rapamycin (mTOR) inhibitors experience a reduction in cutaneous carcinogenesis by an estimated 50% or more compared with calcineurin inhibitors. While randomized trials are running, organ transplant recipients are frequently switched from calcineurin inhibitors to mTOR inhibitors when cutaneous carcinogenesis increases.Objectives To slow carcinogenesis in our patient, a heart transplant recipient with a neuropathic diabetic foot syndrome who had developed cutaneous carcinogenesis at a rate of more than 20 squamous cell carcinomas (SCC) annually.Methods The patient's immunosuppression was switched from the calcineurin inhibitor ciclosporin to the mTOR inhibitor everolimus.Results Carcinogenesis slowed to six SCC annually; however, he developed recalcitrant diabetic foot ulcers which were purely neuropathic and nonangiopathic, and a limb-threatening fistulating necrotic erysipelas of the right leg. Both sites responded poorly to antibiotic therapy, offloading and debridement. This skin fistula became chronic and some toes were at risk for minor amputation. In view of the propensity for mTOR inhibitors to impair would healing, immunosuppression was switched back to ciclosporin. All wounds healed rapidly, but skin carcinogenesis rose to former levels.Conclusions This case impressively illustrates the clinical dilemma for mTOR inhibitor use where benefit in carcinogenesis is counterbalanced by impairment in wound healing. Changes in immunosuppressive regimens should thus be made on an individual basis with careful consideration of the relative risks.