The BUILT study: a single-center 5-year experience of Lung Cancer screening in Taiwan

Background: There are no uniform guidelines on low-dose computed tomography (LDCT) follow-up in lung cancer screening. Few studies have analyzed the incidental abnormalities and role of tumor markers in lung cancer screening. The purpose of this study was to investigate the diagnostic performance of LDCT, optimal follow-up duration, incidental findings, and role of tumor markers in diagnosing lung cancer.Methods: We retrospectively analyzed subjects who underwent their first LDCT in Taipei Tzu Chi Hospital between September 1, 2015, and August 31, 2016. All chest CT scans until August 31, 2020, were recorded. A non-calcified nodule with a diameter ≥2 mm on LDCT was defined as a positive result. We extracted the data, including possible risk factors of lung cancer and follow-up outcomes.Results: A total of 1502 subjects were recruited. Of the 38 subjects who underwent biopsy, 31 had confirmed lung cancer. Lung cancer in all patients was diagnosed within 4 years. Univariate logistic regression analysis revealed that a family history of lung cancer in first-degree relatives and abnormal serum carcinoembryonic antigen (CEA) levels were the significant risk factors for lung cancer. A cumulative lung cancer incidence of 54.7 patients per 1000 person-years was determined solely via radiological follow-up. In total, 271 (18%) subjects exhibited incidental findings on baseline LDCT.Conclusion: The overall lung cancer detection rate in this study was 2.1% in the 5-year study period. A family history of lung cancer and abnormal serum CEA levels are important risk factors for lung cancer. A minimum of 4-year follow-up is required to track suspicious nodules. A purely radiological follow-up detects a high incidence of lung cancer.     

Detection of Pneumocystis jirovecii by PCR in patients with lung cancer: A preliminary study

IntroductionInfection complications in lung cancer (LC), one of the most common cancers in the world, are still among the most important causes of death. Of them, P. jirovecii, which is as an opportunistic infection, causes a life-threatening type of pneumonia in cancer patients. This preliminary study aimed to determine the incidence and clinical status of P. jirovecii by PCR in lung cancer patients compared to the conventional method.Material and methodsSixty-nine lung cancer patients and fSorty healthy individuals were included in the study. After sociodemographical and clinical features were recorded, sputum samples were collected from attenders. Firstly, microscopic examination was made with Gomori's methenamine silver stain and then PCR was performed.ResultsP. jirovecii was detected in three of 69 lung cancer patients by PCR (4.3%), but not by microscopy. However, healthy individuals were negative for P. jirovecii by both methods. Based on clinical and radiological findings, P. jirovecii was evaluated as probable infection in one patient and colonization in the other two patients. Although PCR is more sensitive than conventional staining methods, it cannot distinguish probable and proven infections from pulmonary colonization.DiscussionIt is important to evaluate the decision of infection together with laboratory, clinical and radiological findings. Moreover, PCR may enable to know the colonization and to take precautions such as prophylaxis, due to the risk of colonization turning into an infection in immunocompromised patient groups. Further studies involving larger populations and evaluating the colonization-infection relationship in patients with solid tumors are needed.     

循环肿瘤细胞在肺癌诊疗中的临床研究进展

肺癌现已成为发病率及致死率最高的恶性肿瘤,且呈逐年增高趋势,给人类的身体健康及生命安全带来严重威胁。肺癌的复发与转移是导致患者死亡的最主要原因,可能与循环肿瘤细胞（CTCs）进入血液存在一定关系,CTCs在肺癌患者的早期诊断、治疗指导、疗效评估及预后等方面具有十分重要的作用。本文就CTCs在肺癌诊疗中临床应用及研究进展进行综述。     

Predictive Success Factors for CT-Guided Fine Needle Aspiration Biopsy of Pulmonary Lesions

OBJECTIVE:

Computed tomography-guided percutaneous fine needle aspiration biopsy of lung lesions is a simple, safe and reproducible procedure. Currently, it is widely used to diagnose lung lesions. However, different factors can influence the success rates of this procedure. The purpose of this study was to determine the influence of radiological and procedural characteristics in predicting the success rates of computed tomography-guided fine needle aspiration biopsy of lung lesions.

SUBJECTS AND METHODS:

A retrospective study was developed and involved 340 patients who were submitted to a consecutive series of 362 computed tomography-guided fine needle aspiration biopsies of lung lesions, between July 1996 and June 2004, using 22-gauge needles (Chiba). Variables such as the radiological characteristics of the lesions, secondary pulmonary radiological findings, and procedural techniques were studied.

RESULTS:

For this study, 304 (84%) fine needle aspiration biopsies of lung lesions provided sufficient material for cytological evaluation. The variables that predicted sufficient material for cytological evaluation were lesions larger than 40 mm (p=0.02), lesions on the superior lung lobes (p=0.02), and suspicion of primary lung malignancy (p=0.03). From the multivariate analysis, the only predictive variable for success of the biopsies was localization on the superior lobes (p=0.01).

CONCLUSIONS:

Computed tomography-guided percutaneous fine needle aspiration biopsy of lung lesions showed greater rates of success in biopsies performed in patients with suspicion of primary lung malignancy, with lesions located in the superior lobes, and that have diameters equal to and larger than 40 mm.     

CT‐guided aspiration cytology of advanced silicosis and confirmation of the deposited zeolite nano particles through X ray diffraction: A novel approach

Silicosis is a common occupational lung disease, resulting in fibrotic nodular lesions in the upper lobes of the lung parenchyma. Most of the pneumoconioses are diagnosed on the basis of relevant history and clinico‐radiological correlation. Image‐guided aspiration cytology appears to be poorly yielding and is not usually considered as a diagnostic modality. However, silicosis may sometimes offer a diagnostic challenge because of its radiological resemblance and clinical overlap with pulmonary tuberculosis and neoplastic lesions. We present a unique situation where image‐guided fine needle aspiration cytology (FNAC) has been advised on the basis of nodular upper lobe opacities. The cytology smears revealed hypocellular granular material, while phase contrast and polarized light microscopy highlighted crystalline particles. History of silica dust exposure long back was available after the cytological evaluation, suggesting the diagnosis of pulmonary silicosis. X ray diffraction (XRD) crystallography was also possible on cytology smears, confirming zeolite nano particles of size as small as 40 ? 50 nm as the concerned agent for the first time. Cytological evaluation by phase contrast and polarized light microscopy may be useful for the confirmation of silicosis, supplemented by clinical history and radiological evaluation. XRD on smears may help in determination of chemical nature and particle size. Diagn. Cytopathol. 2016;44:246–249. © 2015 Wiley Periodicals, Inc.     

NTCP modelling and pulmonary function tests evaluation for the prediction of radiation induced pneumonitis in non-small-cell lung cancer radiotherapy

This work aims to evaluate the predictive strength of the relative seriality, parallel and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis (RP), in a group of patients following lung cancer radiotherapy and also to examine their correlation with pulmonary function tests (PFTs). The study was based on 47 patients who received radiation therapy for stage III non-small-cell lung cancer. For each patient, lung dose volume histograms (DVHs) and the clinical treatment outcome were available. Clinical symptoms, radiological findings and pulmonary function tests incorporated in a post-treatment follow-up period of 18 months were used to assess the manifestation of radiation induced complications. Thirteen of the 47 patients were scored as having radiation induced pneumonitis, with RTOG criteria grade 3 and 28 of the 47 with RTOG criteria grade 2. Using this material, different methods of estimating the likelihood of radiation effects were evaluated, by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Lungs were evaluated as a paired organ as well as individual lungs. Of the NTCP models examined in the overall group considering the dose distribution in the ipsilateral lung, all models were able to predict radiation induced pneumonitis only in the case of grade 2 radiation pneumonitis score, with the LKB model giving the best results (chi2-test: probability of agreement between the observed and predicted results Pchi(chi2)=0.524 using the 0.05 significance level). The NTCP modelling considering lungs as a paired organ did not give statistically acceptable results. In the case of lung cancer radiotherapy, the application of different published radiobiological parameters alters the NTCP results, but not excessively as in the case of breast cancer radiotherapy. In this relatively small group of lung cancer patients, no positive statistical correlation could be established between the incidence of radiation pneumonitis as estimated by NTCP models and the pulmonary function test evaluation. However, the use of PFTs as markers or predictors for the incidence or severity of radiation induced pneumonitis must be investigated further.     

bag-1和Chemerin在肺癌临床诊断中的意义

目的评价肺癌患者血清bag-1和Chemerin在临床诊断中的意义。方法采用ELISA法对2009年1月至2011年12月在本院胸心外科接受手术治疗经病理组织检查确诊的56例I～Ⅱ期肺癌患者和60名健康体检者的外周血清进行bag．1、Chemerin蛋白浓度检测。结果肺癌患者外周血bag．1和Chemerin的浓度分别为（32．53±4．22）pg／ml、（54．61±6．78）pg／ml,显著高于健康体检者的（9．49±2．72）pg／ml、（10．23±4．74）pg／ml,差异有统计学意义（P〈0．01）。诊断肺癌bag-1和Chemerin的灵敏度分别为63．5％、67．3％,特异度分别为57．2％、60．4％,阳性拟然比分别为1．48、1．70。两者联合检测的灵敏度、特异度、阳性拟然比分别为89．7％、91．9％、11．07,均高于单检的灵敏度、特异度、阳性拟然比,差异有统计学意义（P〈0．05）。结论bag-1和Chemerin在肺癌诊断中有较高的临床价值。     

突变型p53、VEGF在肺癌中的表达与预后的关系

肺癌的发生、转移和预后与突变型p53、VEGF表达密切相关.突变型P53、VEGF在肺癌组织中高表达,阳性表达明显高于正常的肺组织,两者可以作为评估肺癌生物学行为和预后的指标.突变型P53与VEGF在肺癌中表达有相关性,在促进肺癌新生血管形成的机制中可能存在协同作用.     

A critical appraisal of prognostic and predictive factors for common lung cancers

The outlook for patients with lung cancer remains poor despite advances in the understanding of the pathology and biology of this disease. To optimize treatment protocols prognostic data are essential. The current era with molecular research on mRNA expression analysis and proteomics will lead to a plethora of new molecular markers, which are likely to be correlated, at least in part, with each other and with disease activity, progression and survival. However, although the number of prognostic factors analysed in published systematic reviews on lung cancer is large, the scope of these factors in individual studies is often narrow. In daily practice prognostic factors other than general TNM staging are not implemented. To assess the efficacy of new prognostic factors for the management of individual patients with non-small cell lung cancer, studies with clinically relevant modelling are required. In this review arguments are provided to use a model combining radiological and histopathological growth rate, histopathological diagnosis and molecular characteristics as markers for metastatic capacity, tumour volume doubling time and expected response to targeted therapy. This may reveal time-related predictive information useful for treatment guidance of the individual patient.     

肺干细胞、肺癌干细胞与肺癌

背景：随着肿瘤干细胞理论的出现,近年来通过杀死肿瘤干细胞而治疗肿瘤的研究逐渐兴起,并取得一定的进展。 目的：综述肺干细胞、肺癌干细胞及肺癌的研究进展。 方法：应用计算机检索中国全文期刊数据库及PubMed相关文献,检索词分别为“肺癌干细胞、肺癌、肺干细胞”,“lung stem cell,lung cancer stem cell,lung cancer,cancer stem cell”,并限定语言为英语和中文,最终入选32篇文章进行综述。 结果与结论：肺癌干细胞可能起源于正常肺组织干细胞,而肺癌干细胞可能是肺癌发生的重要因素。随着对肺癌干细胞研究的深入,肺癌治疗将会进入一个崭新的阶段。     

青年肺癌与老年肺癌的研究现状

肺癌是目前发病率和死亡率最高的恶性肿瘤之一,在肺癌的发病与诊治过程中,年龄是其中的一个重要影响因素,不同年龄的肺癌在临床特点、治疗、预后方面都存在一定的差异。本文主要分析青年肺癌与老年肺癌的流行病学特征、临床表现与诊治情况以及预后特点,旨在为肺癌的个性化治疗提供参考依据。     

Clinical significance of the tumor markers CYFRA 21-1 and neuron-specific enolase in lung cancer

The diagnostic validity of CYFRA 21-1 and neuron-specific enolase is assessed in patients with lung cancer. Serum contents of CYFRA 21-1 and neuron-specific enolase are increased, respectively, in 74 and 67% of patients with various histological variants of lung cancer. Diagnostic sensitivity of CYFRA was 77.2% in lung cancer other than the small cell variant and 76% in small cell lung cancer. A correlation between the CYFRA content and the tumor size in patients with squamous and other than small cell lung cancer is demonstrated. In patients with spread small cell cancer, serum enolase content tends to increase compared with that in patients with localized small cell cancer. Both CYFRA and enolase are sensitive lung tumor markers in the diagnostics and evaluation of the extent of tumor spread. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 98–100, January, 1997     

Notch信号通路及其在肺癌发生中的作用

Notch信号通路存在于多种动物体内,是许多细胞信号转导通路的交汇点,不仅对正常组织、细胞的分化、发育起重要作用,而且和一些肿瘤的发生、发展相关。Notch信号在肺癌中的作用多样，在不同类型肺癌中呈现出不同的促癌或抑癌功能。了解Notch和肺癌的关系有利于进一步阐明肺癌发生机制,提出预防和治疗肺癌的新途径，为肿瘤基因治疗提供一个新的有希望的靶点。     

Hypersensitivity pneumonia: the role of lung biopsy in diagnosis and management

Hypersensitivity pneumonia is a form of diffuse interstitial lung disease resulting from sensitization to an inhaled antigen. Clinical and radiological features are relatively nonspecific, overlapping significantly with other forms of diffuse interstitial lung disease. Establishing the diagnosis in the absence of lung biopsy is challenging and is heavily dependent on being able to identify a specific antigenic exposure. Lung biopsy is especially important in diagnosing hypersensitivity pneumonia in patients for whom no incriminating exposure has been elucidated. Surgical lung biopsies show a classical combination of findings in the majority of patients, which include an airway-centered, variably cellular chronic interstitial pneumonia, a lymphocyte-rich chronic bronchiolitis, and poorly formed non-necrotizing granulomas distributed mainly within the peribronchiolar interstitium. The bronchiolitis may include variable degrees of peribronchiolar fibrosis and hyperplasia of the bronchiolar epithelium ('peribronchiolar metaplasia'), a characteristic but a nonspecific finding. In some patients, granulomatous inflammation may be lacking, resulting in a histological appearance resembling nonspecific interstitial pneumonia. Late-stage fibrotic hypersensitivity pneumonia results in clinical, radiological, and histological findings that closely mimic usual interstitial pneumonia. The presence of established collagen fibrosis, especially when associated with architectural distortion in the form of honeycomb change, is associated with shorter survivals.     

The assessment of lead time and length bias in the evaluation of screening programmes

The evaluation of screening programmes for cancer is discussed with particular reference to lead time and length bias. The epidemiological approach, concentrating on the population screened instead of the cases detected, leads to a useful evaluation of the concepts of lead time and length bias, being closely related to the natural history of the disease in question. This is shown by reviewing screening programmes for these different diseases: breast cancer, lung cancer and cervical cancer.     

非小细胞肺癌患者血清中纤维母细胞生长因子受体表达意义及其与血清肿瘤标志物的相关性研究

目的 研究非小细胞肺癌患者血清中纤维母细胞生长因子受体(fibroblast growth factor receptor-1,FGFR1)表达意义及其与血清肿瘤标志物的相关性。方法 研究对象选取我院收治的非小细胞肺癌患者65例,并选取同期14例肺良性病变患者、25例原发性肝癌患者及35名健康体检者作为对照组,应用实时荧光定量聚合酶链反应法检测各组受试者血清FGFR1 DNA表达水平,采用电化学发光法检测肺癌患者血清癌胚抗原(carcinoembryonic antigen,CEA)、细胞角蛋白(cytokeratin-19-fragment,Cyfra21-1)以及神经特异性烯醇化酶(neuron specific enolase,NSE)水平。比较各组血清FGFR1 DNA表达水平的差异并进行ROC曲线分析血清FGFR1水平诊断肺癌的准确性。采用Pearson相关性分析法分析肺癌患者血清FGFR1表达水平与CEA、Cyfra21-1及NSE的相关性。结果 单因素方差分析显示:各组血清FGFR1 DNA表达水平差异具有统计学意义(F=249.38,P<0.001);且肺癌患者血清FGFR1 DNA表达水平明显高于良性病变组(t=11.41,P<0.01)、肝癌组(t=9.09,P<0.01)及健康组(t=36.96,P<0.01);不同临床特征肺癌患者血清FGFR1 DNA表达水平具有明显差异,其中鳞癌患者血清FGFR1表达水平明显高于腺癌和其他肺癌(F=45.22,P<0.001),晚期(Ⅲ~Ⅳ)肺癌患者明显高于早期(Ⅰ~Ⅱ)肺癌患者(F=171.11,P<0.001),淋巴结转移阳性患者明显高于阴性患者(F=125.34,P<0.001)。ROC曲线分析显示:AUC=0.904>0.5具有诊断价值,最佳诊断临界值为1.79×10^5copies/μL,灵敏度为94.65%,特异性为82.76%。Pearson相关性分析显示:鳞癌患者血清FGFR1表达与CEA、Cyfra21-1及NSE均呈明显正相关(P<0.05),其中与Cyfra21-1的相关性最大(r=0.528);腺癌患者血清FGFR1表达与CEA呈弱相关关系(r=0.145,P=0.03),与Cyfra21-1、NSE均无明显相关性;其他类型肺癌患者血清FGFR1表达与CEA、Cyfra21-1及NSE均无明显相关性(P>0.05)。结论 肺癌患者血清FGFR1表达具有显著的临床意义,在肺癌的诊断中具有较高的诊断效能,另外FGFR1的表达与血清肿瘤标志物具有明显相关性,进一步表明其在肺癌的诊断、病理分型及预后的评估等方面具有重要临床意义。     

三维适形放疗计划轮照对肺癌剂量分布影响的研究

介绍了肺癌的常规放疗.分析了肺癌三维适形放疗的CT定位和靶区确定、计划的设计、计划的优化、计划的评价,计划的轮照对肺癌正常组织等影响.提出了减少正常组织损伤的方法.     

Comparative oncology of lung tumors

Toxicologic pathologists need to understand the comparative oncology of lung tumors because lung cancer is a common and serious cancer in the human population. Lung cancer in humans is known to be caused by cigarette smoke and a number of other carcinogens in the environment. Animal studies are needed to elucidate possible interactions with other potential carcinogens in environmental or occupational settings. In addition, knowledge of dose-response relationships and potential synergistic effects are needed to minimize harmful effects. Understanding the pathogenesis of common lung tumors will also aid in the prevention, diagnosis and treatment of the disease. Toxicologic pathologists need to remember several important points about lung tumors. The lung cancer response varies among species. Important factors in this variation are the nature of the administered carcinogen, the tissue dose of the carcinogen, the mode of exposure, the sensitivity of the test animal species and the similarity to the human response. Studies of molecular changes are important new tools to understanding lung carcinogenesis. For example, the molecular changes in lung tumors of mice and humans have a number of similarities that may be important in evaluating the significance of compound-induced lung tumors in mice.     

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。