Abstract
背景与目的软脑膜转移(leptomeningeal metastasis, LM)是指恶性肿瘤细胞浸润软脑膜,并在脑脊液(cerebrospinal fluid, CSF)中播散,预后极差,是晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者致死的重要原因之一,因此早期的诊断和及时的治疗具有重要意义,CSF细胞学是LM诊断的金标准,但常常伴随着检测敏感性低、无法评估疗效等问题。本文旨在探讨血清及CSF中肿瘤标志物(tumor markers, TM)在NSCLC伴LM患者诊治的临床价值。方法选取NSCLC伴LM患者19例,另选同期27例神经系统良性肿瘤(nonmalignant neurological diseases, NMNDs)患者作为对照组。观察比较两组患者血清和CSF中癌胚抗原(carbohydrate antigen, CEA)、糖类抗原125(carbohydrate antigen-125, CA125)、细胞角蛋白19片断抗原(cytokeratin 19 fragments, CYFRA21-1)和神经元烯醇化酶(neurone specific enolase, NSE)检测水平和检出阳性率,比较不同组TM的敏感性和特异性,并分析血清与CSF中TM检出情况相关性,最后动态监测2例LM患者血清和CSF中TM水平,分别评估颅外和颅内治疗疗效。结果LM组CSF和血清中TM水平和检出阳性率均高于对照组(P < 0.05),同时LM组CSF中CEA、CYFRA21-1、NSE水平高于血清,差异有统计学意义(P < 0.05)。CSF中TM检出阳性率与血清差异不具有统计学意义(P > 0.05)。CSF中CYFRA21-1敏感性最高(88.2%),CEA特异性最好(92.3%),联合指标中CEA或NSE任一项超过临界值则敏感性和阴性预测值为100%,特异性为74.1%。CYFRA21-1和NSE同时超过临界值时特异性和阳性预测值为100%,敏感性为78.9%。亚组分析显示,CSF细胞学阳性人群TM检出阳性率超过有磁共振成像(magnetic resonance imaging, MRI)异常的人群,但不具有统计学差异(P > 0.05)。LM组血清与CSF中TM检出阳性率不一致。另外,脑室中CSF与腰穿中CSF具有相同的生化性质,动态监测血清和CSF中TM浓度,可分别评估颅外和颅内病灶的疗效。结论血清和CSF中TM为NSCLC伴LM患者增加了一个早期辅助诊断指标,动态监测可评估治疗疗效,值得临床推广应用。
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