低剂量螺旋CT扫描联合血清p16基因甲基化检测在肺癌早期诊断中的应用

目的研究在无症状的肺癌高危人群中利用低剂量CT（LDCT）联合血清p16基因甲基化检测进行肺癌早期诊断的可行性。方法肺癌高危人群入组标准：男性，年龄55～75岁；吸烟指数≥400支／年，目前仍在吸烟或戒烟不超过10年。共893例受检者被随机分为两组。一组为447例（LDCT—p16组），平均年龄66岁，进行LDCT联合血清p16基因甲基化检测；另一组为446例（CXR组），平均年龄67岁，接受后前位胸片检查。两组检查阳性病例将接受进一步组织病理学检查。并分别统计两组阳性结节检出率及肺癌检出率，并行X2检验。结果LDCT—p16组与CXR组分别有96．8％和92．8％的受检者完成了检查。LDCT—p16组中1113％病人可疑肺癌，明显高于CXR组的6．5％（P〈0．05）。其中LDCT—p16组中有7例，CXR组中有2例确诊为肺癌。LDCT—p16组肺癌检出率高于CXR组，但无统计学意义（P〉0．05）。结论低剂量CT联合血清p16基因甲基化检测是一种敏感、安全、可行的筛查早期肺癌的方法，能够取代胸片筛查早期肺癌。     

Lung cancer screening: history,current perspectives,and future directions

Lung cancer has remained the leading cause of death worldwide among all cancers. The dismal 5-year survival rate of 16% is in part due to the lack of symptoms during early stages and lack of an effective screening test until recently. Chest X-ray and sputum cytology were studied extensively as potential screening tests for lung cancer and were conclusively proven to be of no value. Subsequently, a number of studies compared computed tomography (CT) with the chest X-ray. These studies did identify lung cancer in earlier stages. However, they were not designed to prove a reduction in mortality. Later trials have focused on low-dose CT (LDCT) as a screening tool. The largest US trial – the National Lung Screening Trial (NLST) – enrolled approximately 54,000 patients and revealed a 20% reduction in mortality. While a role for LDCT in lung cancer screening has been established, the issues of high false positive rates, radiation risk, and cost effectiveness still need to be addressed. The guidelines of the international organizations that now include LDCT in lung cancer screening are reviewed. Other methods that may improve earlier detection such as positron emission tomography, autofluorescence bronchoscopy, and molecular biomarkers are also discussed.     

Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center

To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with >or=45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (>or=20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.     

The role of screening expectations in modifying short–term psychological responses to low-dose computed tomography lung cancer screening among high-risk individuals

ObjectiveThis study aimed to examine the relationship between pre-screening expectations and psychological responses to low-dose computerised tomography (LDCT) screening among high-risk individuals in the United Kingdom Lung Cancer Screening (UKLS) pilot trial.MethodsPrior to screening, high-risk individuals randomised into the intervention arm of the UKLS were asked about their expected screening test result. Their actual LDCT scan result was compared with their baseline screening expectation to determine the level of congruence. Levels of concern about and perceived accuracy of the result were assessed in a questionnaire two weeks following receipt of their test result.ResultsThe sample included 1589 participants. Regardless of their expected results, patients who required follow-up investigations after their initial LDCT scan were the most concerned about their result (p < 0.001). Participants who expected to require follow-up, but did not need it, perceived the test to be least accurate (p = 0.006).ConclusionsLung cancer screening participants who require follow-up or who have unexpected negative results can be identified for supportive interventions.Practical Implications: These findings can be used to ensure that any future LDCT lung cancer screening programme is tailored to identify and support those high-risk individuals who may benefit from additional help.     

肺部磨玻璃结节的CT特征与治疗策略进展

原发性肺癌是位居我国癌症死亡首位的恶性肿瘤,早发现并及时治疗的患者可以获得良好的效果。低剂量CT（LDCT）筛查的运用使得早期肺癌能够被及时发现,随着LDCT筛查的普及越来越多肺内磨玻璃结节（GGN）被发现。表现为GGN的周围型肺癌术前明确病理学诊断较为困难,而GGN的性质对于手术决策有重要参考意义,因此通过分析影像学特征来推断病变性质并作出合理的治疗策略十分重要。     

肺癌血清肿瘤标记物的联合检测及其临床意义

目的评价CEA、NSE、CYFRA21-1联合检测对肺癌与良性肺部疾病鉴别诊断的价值。方法应用电化学发光法（ECLIA）检测经病理确诊的56例肺癌、41例良性肺部疾病和30例正常体检者血清中癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）和细胞角蛋白21—1（CYFRA21-1）的含量。结果肺癌组CEA、NSE、CYFRA21—1测定水平明显高于肺良性病变组和正常对照组,差异具有统计学意义（P〈0．05）;CEA、NSE、CYFRA21—1对肺癌的敏感性分别为51．79％、44．64％、55．36％,特异性分别为92．96％、90．14％、88．73％;CEA、NSE、CYFRA21-1三项联合检测对肺癌的敏感性与特异性分别为92．86％和94．37％。结论CEA、NSE、CYFRA21-1三项肿瘤标记物联合检测明显提高肺癌诊断的阳性率,有助于肺癌的预测和鉴别诊断。     

CA19-9、CA125、CEA和CYFRA21-1检测对肺腺癌患者骨转移的诊断价值分析

目的 研究CA19-9、CA125、CEA和细胞角蛋白19片段(CYFRA 21-1)检测对肺腺癌患者骨转移的诊断价值,为临床诊断提供参考.方法 选取2015年1月至2015年12月在我院住院治疗的肺腺癌患者90例,对所有患者行CA19-9、CA125、CEA、CYFRA 21-1检测以及骨显像检查,对比骨转移患者与非骨转移患者四项肿瘤标志物检测情况及阳性分布.结果 骨显像阳性患者血清中CA19-9、CA125、CEA以及CYFRA 21-1四项肿瘤标志物的检测结果以及阳性率均显著高于骨显像阴性患者,且差异均具有统计学意义(P＜0.05);四项肿瘤标志物从正常浓度到1～3倍浓度再到大于3倍浓度患者的骨显像阳性率呈阶梯式上升.结论 CA19-9、CA125、CEA以及CYFRA 21-1四项肿瘤标志物在肺癌骨转移患者中的阳性率均较高,可在监测肺癌骨转移时作为参考指标.     

血清肿瘤标志物CEA、CA724、CA242、CA19-9联合检测诊断肺癌的临床价值分析

目的 分析血清肿瘤标志物癌胚抗原(CEA)、糖类抗原724(CA724)、糖类抗原242(CA242)、糖类抗原19-9(CA19-9)联合检测与肺癌诊断及预后的相关性.方法 选取2014年5月至2017年1月我院收治的肺癌患者120例为研究对象,并纳入观察组,以同期入院体检的良性肺疾病患者55例为对照组,测定两组血清CEA、CA724、CA242、CA19-9水平,对比四种肿瘤标志物在不同病理类型肺癌中表达水平,分析CEA、CA724、CA242、CA19-9联合检测与单项、2联、3联检测诊断肺癌的灵敏度、特异度、准确度、阳性预测值、阴性预测值,比较CEA、CA724、CA242、CA19-9阳性或阴性患者在预后随访中无复发生存率、远处转移率.结果 观察组血清CEA(30.24±1.75)μg/L、CA724(14.85±1.11)kU/L、CA242(38.18±1.05)kU/L、CA19-9(41.24±1.57)kU/L均较对照组高(P<0.05);CEA、CA242在腺癌中表达水平最高,CA724、CA19-9在腺癌与鳞癌中表达水平差异无统计学意义(P>0.05);CEA、CA724、CA242、CA19-9联合检测诊断肺癌的灵敏度98.18%、准确度80.00%、阴性预测值80.00%,均高于上述指标单项或2联、3联检测(P<0.05);CEA、CA724、CA242、CA19-9阳性患者与阴性患者比较,无复发生存率明显较低,远处转移率显著较高(P<0.05).结论 血清肿瘤标志物CEA、CA724、CA242、CA19-9联合检测诊断肺癌的灵敏度、准确度较单项、2联及3联检测明显提高,且上述指标可用于预测预后,值得在临床推广应用.     

Early Lung Cancer Detection Using the Self-Evaluation Scoring Questionnaire and Chest Digital Radiography: A 3-Year Follow-up Study in China

The standard definition of high-risk individuals for lung cancer was not uniform and the value of chest digital radiography (DR) in lung cancer screening was still unproven. The aim of this study was to assess whether the original questionnaire named as “Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer” combined with DR examinations could detect early stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer had been designed in previous studies. Subjects with scores over 116 points were regarded as high-risk individuals and underwent the current DR scans at least once a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of the scoring questionnaire combined with DR scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were diagnosed with lung cancer in the first, second, and third year, respectively, indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31) of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the 31 cases, 28 were defined as detected cancers, while the other three were interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with DR scans is a cost-effective and safe approach to detect early stage of lung cancer.     

Cancer detection and prevention

Studies were performed on cancer detection and prevention in the high cancer risk group. To improve the screening method in the diagnosis of unspecified cancer, a modified combination assay was devised using a combination of several tumor markers and adding risk factors of malignancies obtainable from blood samples. Five tumor markers, AFP, CEA, CA 19-9, DUPAN-2 and CA 125 were determined simultaneously in each serum sample obtained from 54 patients with various cancer diseases. A modified combination assay was also examined using the risk factors of malignancies, pepsinogen I/II ratio together with 5 tumor markers. Detection rate was elevated to 68.5% by a combination assay using 5 tumor markers. Detection rate by modified combination assay using the risk factor (pepsinogen I/II ratio) together with 5 tumor markers was further improved to 88.8% without decreasing the specificity. The modified combination assay is easy in practice and expected to contribute in the screening of unspecified cancer diseases.     

Comparison of serum levels of beta2-microglobulin and carcino-embryonic antigen in the follow-up of lung cancer (author's transl)]

Serum levels of carcino-embryonic antigen (CEA) and beta2-microglobulin (beta2m) were assayed on 133 sera during follow-up of 31 patients with lung carcinoma (squamous cell ca. without recurrence : 2, squamous cell ca. with recurrence : 11, anaplastic cell ca. : 4, adenocarcinoma : 2, unclassifiable : 5). Normal creatinine (less than or equal to 12 mg/l) levels were found in all sera. CEA and beta2m levels showed no correlation nor in these groups, nor in the whole. The squamous cell carcinomas with recurrence showed the largest dispersion for CEA as for beta2m levels. However, the trends of serial beta2m values did not correlate with clinical features. Increasing or decreasing levels of CEA and beta2m levels showed no correlation in the whole nor in patients undergoing radiotherapy. In our experience, beta2m levels failed to correlate with clinical findings during the follow-up of lung cancer patients.     

Low-dose computed tomography screening reduces lung cancer mortality

Lung cancer causes an estimated 1.6 million deaths each year, being the leading cause of cancer-related deaths in the world. Late diagnosis and, in some cases, the high aggressiveness of the tumour result in low overall five-year survival rates of 12% among men and 7% among women. The cure is most likely in early-stage disease. The poor outcomes of treatment in lung cancer resulting from the fact that most cases are diagnosed in the advanced stage of the disease justify the implementation of an optimal lung cancer prevention in the form of smoking cessation and screening programmes that would offer a chance to detect early stages of the disease, while fitting within specific economic constraints. The National Lung Screening Trial (NLST) – the largest and most expensive randomised, clinical trial in the USA demonstrated a 20% mortality rate reduction in patients who had undergone chest low-dose computed tomography (LDCT) screening, as compared to patients screened with a conventional chest X-ray. Results of the NLST enabled the implementation of lung cancer screening programme among highrisk patients in the USA and parts of China. In 2017, recommendations of the European Society of Thoracic Surgeons also strongly recommend an implementation of a screening programme in the EU. Further studies of improved lung cancer risk assessment scores and of effective molecular markers should intensify in order to reduce all potential harms to the high-risk group and to increase cost-effectiveness of the screening.     

血清NSE、CEA、CYFRA21-1联检对肺癌的诊断价值

目的:探讨联检血清肿瘤标志物神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)对肺癌的诊断价值.方法:采用电化学发光法检测102例肺癌患者和50例良性肺病患者血清NSE、CEA、CYFRA21-1的含量.结果:肺癌患者血清NSE、CEA、CYFRA21-1水平均明显高于良性肺病患者,差异有统计学意义(P＜0.01).三种血清标志物的分布有明显的病理倾向性.NSE在小细胞癌中表达水平较高,其敏感性为59.4%; CEA在腺癌中表达水平较高,其敏感性为61.5%;而CYFRA21-1则在鳞癌中表达水平较高,其敏感性为64.5%.联检可提高检测肺癌的敏感性.结论:三种血清肿瘤标志物对于肺癌的辅助诊断有一定的临床意义,联检NSE、CEA和CYFRA21-1可以提高肺癌的诊断敏感性,为肺癌的早期诊断、病理分型提供可靠的依据.     

基于临床数据的胃癌筛查模型研究

目的:利用临床数据,通过机器学习建立辅助筛选模型,以提高胃癌早期诊断水平。方法:以5 585例胃癌（ICD编码为C16*,A组）患者为研究对象,并从57 657例非胃部恶性肿瘤（ICD编码为C*,除C16*外）中随机选择6 000例（B组）,从47 225例健康体检者中随机选择6 000例非恶性肿瘤（C组）,作为对照。从临床数据中抽取人口学（性别、年龄）、实验室检测（血常规检测、血脂/肝功能、肿瘤相关标志物、Hp等）等信息。利用Pearson相关性分析,对各指标与诊断之间的相关性进行分析。采用独立样本t检验,检测各指标的组间差异性。选择性别、年龄、癌胚抗原（CEA）、粪隐血（FOB）等53项指标作为决策变量,采用决策树算法C5.0,建立胃癌辅助筛查模型。结果:年龄、CEA、CA153等指标与胃癌显著相关（P<0.05）。在A组-B组、B组-C组、A组-C组中,存在组间差异性的指标不相同。通过数据挖掘,得到了包含51条规则的胃癌筛查模型。模型中重要性位于前10的指标依次为CA199、CA153、CEA等。对于训练集、测试集,模型的准确率分别为89.58%、89.14%,曲线下面积为0.809。结论:通过临床数据分析,可以确定胃癌早期诊断的重要指标。利用数据挖掘方法,基于临床数据可以建立胃癌筛查辅助模型,对于胃癌筛查具有良好的辅助价值。     

胸水和血清中CEA、CYFRA21-1、TPS联合检测对良恶性胸水及肺癌的诊断价值

目的:探讨胸水和血清肿瘤标志物癌胚抗原(CEA),细胞角蛋白片段21-1(CYFRA21-1) ,组织多肽特异性抗原(TPS)在肺癌诊断中的临床意义.方法:应用电化学发光法和ELISA分别测定78例肺癌患者,45例肺部良性疾病胸水和血清CEA、CYFRA21-1、TPS水平,结果:肺癌组胸水CEA、CYFRA21-1、TPS水平明显高于良性疾病胸水组(P<0.01);肺癌组血清CEA、TPS水平明显高于良性疾病血清组(P<0.05,P<0.01);在不同病理类型肺癌中3种肺癌肿瘤标志物升高的程度均有所不同;恶性胸水组中肿瘤标志物的含量与同期血清中的含量相比,出现更早且浓度更高,尤以TPS升高最为明显.单项检测中,胸水TPS的敏感性最高,联合检测中,胸水TPS CYFRA21-1 CEA的敏感性和准确性最高.结论:CEA、CYFRA21-1、TPS三项联合检测对良恶性胸水的鉴别有较好的诊断价值. 胸水中3种肺癌标志物的联合检测较血清有更高的敏感性,准确性.其临床价值优于血清.     

肿瘤标志物联检对常见肿瘤诊断的评价

目的:探讨用肿瘤标志物联检来提高常见肿瘤的检出率。方法:将甲胎蛋白(AFP)、癌胚抗原(CEA)、铁蛋白(SF)、唾液酸(TSA)组成为肿瘤标志物———“肿瘤组合”,用放射免疫分析检测AFP、CEA、SF,用化学法检测TSA。将临床常见肿瘤病人作“肿瘤组合”测定,结果经统计分析作肿瘤诊断的评价。结果:“肿瘤组合”对肿瘤组的阳性率为89 1%。常见肿瘤的阳性率分别为原发性肝癌95 2%、肺癌92 6%、胃癌88 5%、直结肠癌83 3%、乳腺癌84 2%、绒癌90%、卵巢癌88 9%。结论:“肿瘤组合”是一种筛查常见肿瘤的简单、廉价的实验室方法。     

癌胚抗原和铁蛋白对乙状结肠癌的诊断价值评估

目的 探讨血清肿瘤标志物对乙状结肠癌的诊断价值.方法 收集2014年1月至2017年6月在解放军总医院手术治疗的乙状结肠癌患者116例、乙状结肠息肉110例和健康对照者66例的临床资料.对患者基本信息及血清指标进行单因素统计分析,采用ROC曲线及二分类Logistic回归比较单一指标和组合指标的诊断效能.结果 单因素统计分析显示术前血清癌胚抗原(CEA)、CA19-9、CYFRA21-1、铁蛋白(Ferritin)和鳞状上皮细胞癌抗原(SCC)三组间差异有统计学意义(P＜0.05).血清CEA为单一指标中诊断乙状结肠癌最优,ROC曲线下面积(AUC) 0.71 (95％ CI:0.64～0.78),CEA的临界值取3.08μg/L,灵敏度为57.8％、特异性为80.9％.血清CEA+ Ferritin组合较为理想(AUC=0.80,95％ CI:0.74 ～0.85),灵敏度为81.0％,特异性为64.5％,Logistic回归模型对乙状结肠癌的诊断准确率为69.0％.结论 血清癌胚抗原和铁蛋白联合检测是较为理想的肿瘤标志物组合,有助于乙状结肠癌的早期筛查.     

慢性阻塞性肺病及其相关非小细胞肺癌进程与EMT 的相关性研究

目的:通过对相关数据库数据分析,探究EMT 相关调节因子的异常表达与慢性阻塞性肺疾病及其相关非小细胞肺癌的相关性。方法:对NCBI 中GEO 数据库中的若干数据集数据进行表达量分析、生存分析和相关性分析。结果: 研究分析表明,Snai1 等EMT 相关调节因子在非小细胞肺癌患者中存在明显的高表达,而E-cadherin(CDH1)等则表现为明显的低表达。于对大量的COPD 病例样本进行分析,发现部分EMT 相关的分子在COPD 患者中也表现出明显的表达异常,且与非小细胞肺癌患者中的变化相一致。结论:EMT 指标和在COPD 患者中的表达相关性分析表明,EMT 调节因子的异常表达可能与COPD 患者的疾病发展存在一定的相关性。     

血清和肺泡灌洗液中肿瘤标志物检测对肺癌的诊断价值分析

目的：分析血清和肺泡灌洗液中肿瘤标志物对肺癌的诊断价值,研究其表达水平与肺癌的相关性及用于肺癌诊断的可行性。方法：应用流式细胞术检测40例肺癌组和肺良性病变组hnRNPA2/B1的表达情况;同时用化学发光免疫法检测血清肿瘤标志物CEA、NSE、CYFRA21-1和SCCAg的含量。结果：hnRNPA2/B1在肺癌组与肺良性病变组表达率分别为86.01%±32.48%和32.1%±10.02%,差异显著（P〈0.01）。肺癌组hnRNPA2/B1检测阳性率为85%,40例肺癌组样本肿瘤标志物CEA、NSE、CYFRA21-1、SCCAg联检阳性率52.5%,肺泡灌洗液中hnRNPA2/B1的阳性检出率明显高于CEA、NSE、CYFRA21-1及SCCAg四项肿瘤标志物的联检。结论：血清CEA、NSE、CYFRA21-1及SCCAg四项肿瘤标志物联检肺泡灌洗液脱落细胞内hnRN-PA2/B1对肺癌辅助诊断有较大的临床应用价值。     

血清SCC、NSE、CYFRA21-1及CEA联合检测在肺癌诊断中的价值

目的探讨血清SCC、NSE、CYFRA21-1及CEA联合检测在肺癌的诊断价值。方法采用电化学发光免疫分析法测定血清SCC、NSE、CYFRA21-1及CEA水平及其组合,评价其在肺癌诊断中的价值。结果肺癌组四项指标显著高于对照组和肺良性疾病组,差异有统计学意义（P〈0.05）;不同病理类型的肺癌四项检测指标,差异有统计学意义（P〈0.05）;但四项指标联合检测敏感性明显高于任一个单项肿瘤标志物。结论单项肿瘤标志物对肿瘤的诊断价值有限。四项标志物联合检测有利于肺癌的早期诊断。