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肺癌的相关知识(一)

引言

       2012年,全世界大约有180万新发肺癌,估计导致的死亡有160万。肺癌的绝对和相对发病率都显著上升。1953年左右,肺癌成为了男性最常见的癌症死因,1985年又成为了女性主要的癌症死亡原因。目前,男性和女性肺癌死亡人数均开始下降,这反映了吸烟减少。

        肺癌或支气管肺癌指气道或肺实质发生的恶性肿瘤。约95%的肺癌可划分为小细胞肺癌(small cell lung cancer, SCLC)或非小细胞肺癌(non-small cell lung cancer, NSCLC)。这种区分对于肺癌的分期、治疗及预后至关重要。其他细胞类型约肺恶性肿瘤的5%

危险因素

吸烟——许多环境和生活方式因素与之后发生肺癌相关,其中吸烟最为重要。吸烟是肺癌发生的主要危险因素,据估计约占所有肺癌的90%。连续40年每日1包烟且尚未戒烟的人,发生肺癌的风险约是从不吸烟者的20倍。增加吸烟人群肺癌风险的因素包括,吸烟过多时间过长和暴露于石棉等其他致癌因素。因此,最重要的肺癌预防策略是防止人们开始吸烟和劝导吸烟者戒烟。戒烟者发生肺癌的风险低于继续吸烟者;这一获益在30岁以前戒烟者中最为明显。

其他因素——许多其他因素也可能影响肺癌的发生风险:因其他恶性肿瘤接受过放疗(radiation therapy, RT)的患者,其发生第二原发性肺癌的风险可能增加;环境毒素与肺癌风险增加相关,包括暴露于二手烟、石棉、氡、金属(砷、铬和镍)、电离辐射和多环芳烃类;肺纤维化患者的肺癌风险约是一般人群7倍;HIV感染者的肺癌发病率高于未感染的正常人;遗传因素可影响肺癌的发生风险和预后;多种饮食因素(抗氧化物、十字花科蔬菜和植物雌激素)可能降低肺癌风险,但其作用尚未明确。

筛查

CT筛查出的肺癌有很大一部分处于早期,预后良好。美国Medicare和Medicaid医疗保险服务中心(Center for Medicare and Medicaid Service, CMS)同意报销已批准人群的CT筛查费用,批准的筛查人群需满足:年龄55-77岁,无肺癌症状,有30包年吸烟史,未戒烟或戒烟不超过15年。

病理学

肺癌分类应遵照2015WHO制定的原发性肺癌分类标准。

腺癌的相对发病率已明显升高,而NSCLC中的其他类型和SCLC的发病率相应下降。腺癌发病率增加被认为是由于20世纪60年代出现了低焦油过滤香烟,但这一相关性未经证实。

过去对于新诊断的肺癌,病理学上只用区分NSCLC与SCLC,再加上分期,就足以决定治疗方案;但近年来已发生了改变。自2008年以来,研究表明,区分腺癌与鳞状细胞癌(下文简称鳞癌)对于决定期肺癌的最佳治疗有着重要意义。针对特定基因突变的靶向治疗的问世,实现了个性化治疗。如今又开始分析NSCLC的亚型了,因为表皮生长因子受体基因(EGFR)、间变性淋巴瘤激酶基因(ALK)、c-ROS癌基因1(ROS1)的突变不仅能查出,其靶向治疗的缓解率也高于标准化疗。

15%-30%的非亚裔和30%-60%的亚裔腺癌患者携带EGFR基因突变。ALK基因突变见于美国2%-7%NSCLC患者。基于针对这些突变的特异性酪氨酸激酶抑制剂改善了缓解率。

免疫治疗对晚期肺癌具有前景且发展迅速。检查点抑制剂可促进免疫系统将癌细胞识别为外源细胞,并逆转肿瘤驱动的、促进肿瘤生长的免疫系统抑制作用。使用程序性死亡受体1和程序性死亡配体1抗体的临床试验显示,其可显著改善晚期NSCLC患者的生存。

基于突变检测和免疫抑制的个体化处理措施对疑似肺癌病例的初始评估也有影响,因为诊断性取材要足量,以便在查出晚期腺癌时检测各种突变。支气管内超声引导下穿刺抽吸活检、经胸壁穿刺抽吸活检和胸水细胞学检查的标本,如果能查出腺癌,90%以上都足以用于分析突变。

临床表现

大多数肺癌患者在临床就诊时已是晚期,症状来源于肿瘤的局部效应、区域或远处扩散或与转移无关的远隔效应(副肿瘤综合征),就诊时最常见的症状是咳嗽(55%)、呼吸困难(45%)、疼痛(38%)和体重减轻(36%)。

一、肺癌在胸腔内的效应 

肺癌在胸腔内的效应可引起多种症状,最常见的是咳嗽、咯血、胸痛及呼吸困难。

(一)咳嗽

 50%-75%的肺癌患者在就诊时存在咳嗽,咳嗽最常见于鳞癌和SCLC,因为它们好发于中心气道。如果吸烟者或既往吸烟者新发咳嗽,则应怀疑肺癌。

(二)咯血

 咯血见于20%-50%诊断为肺癌的患者,但该症状最常见的原因是支气管炎。任何量的咯血都会令患者担忧,大量咯血可能导致窒息。

(三)胸痛 

20%-40%的肺癌患者有胸痛,胸痛通常出现于原发瘤的同侧。

(四)呼吸困难 

 呼吸急促是诊断肺癌时的常见症状,见于25%-40%的患者。呼吸困难可能是由于:气道管腔外或腔内梗阻、阻塞性肺炎或肺不张、淋巴管炎性肿瘤转移、肿瘤栓子、气胸、胸腔积液或伴有心包填塞的心包积液。支气管部分阻塞可引起局部哮鸣音,可由患者听到或由临床医生听诊发现,而喘鸣可能是由于更大的气道受阻。

(五)声音嘶哑 

吸烟者持续性声音嘶哑的鉴别诊断包括喉癌和肺癌。肺癌中的持续性声音嘶哑是由于癌症沿喉返神经的走行侵犯该神经。

(六)胸膜受累 

 胸膜受累可表现为无胸腔积液的胸膜增厚,或是恶性胸腔积液。

(七)上腔静脉综合征

上腔静脉阻塞引发的症状通常包括头部胀满感和呼吸困难。体格检查可见颈静脉扩张、胸壁静脉明显、面部水肿和多血质。

二、胸腔外转移 

肺癌可播散到全身任何组织。转移性播散可能导致首发症状,也可能在病程后期出现。远处转移最常见的部位是肝、肾上腺、骨和脑。

三、副肿瘤现象 

肿瘤的副肿瘤效应是与直接侵犯、阻塞和转移无关的远隔效应。

(一)高钙血症 

肺癌患者的高钙血症可能是由于骨转移,少数是由肿瘤分泌的甲状旁腺激素相关蛋白(parathyroid hormone-related protein, PTHrP)、骨化三醇或其他细胞因子,包括破骨细胞活化因子。

(二)SIADH 

 抗利尿激素不适当分泌综合征(syndrome of inappropriate antidiuretic hormone secretion, SIADH)通常由SCLC引起,可导致低钠血症。症状的严重程度与低钠血症的程度及血清钠下降速度有关。症状包括厌食、恶心和呕吐。速发的低钠血症可引起脑水肿。脑水肿的症状可能包括易激惹、躁动、人格改变、意识模糊、昏迷、癫痫发作和呼吸骤停。

(三)神经系统 

肺癌是最常导致神经副肿瘤综合征的癌症,其中多为SCLC所致。神经副肿瘤综合征被认为是免疫介导的,已在许多例子中发现了自身抗体。这些多种多样的神经系统表现包括但不限于:Lambert-Eaton肌无力综合征(Lambert-Eaton myasthenic syndrome, LEMS)、小脑性共济失调、感觉神经病变、边缘叶脑炎、脑脊髓炎、自主神经病变、视网膜病变以及眼阵挛-肌阵挛。

(四)血液系统表现

 肺癌患者可出现多种血液系统异常,包括:贫血、白细胞增多、血小板增多、嗜酸性粒细胞增多、高凝状态性疾病、Trousseau综合征(游走性血栓性浅静脉炎)深静脉血栓形成和血栓栓塞弥漫性血管内凝血血栓性微血管病和非血栓性微血管病。

(五)肥大性骨关节病

肺性肥大性骨关节病(hypertrophic pulmonary osteoarthropathy, HPO)是指肺癌或其他肺病伴随的杵状指和管状骨骨膜增生。HPO的临床特征是对称性疼痛性关节病,通常累及踝、膝、腕、肘关节。掌骨、跖骨和指()骨也可能受累。

(六)皮肌炎和多发性肌炎

皮肌炎和多发性肌炎是炎性肌病的2种不同形式,临床上都表现为肌无力。这些炎性肌病可以是肺癌的首发症状,也可以在病程后期出现。

(七)库欣综合征 

 促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)异位分泌可引起库欣综合征。患者通常表现为肌无力、体重减轻、高血压、多毛和骨质疏松。低血钾性碱中毒和高血糖也常见。

 

 

 

 

 

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