Lung cancer screening--present status and the problems

For the counter measure having been indicated against increasing mortality rate in lung cancer cases, indication of lung cancer screening was started in 1987 in line with the law of insurance established for old aged people. In order to decrease the death rate in cases with lung cancer, methods of the counter measure were established for early detection of lung cancer by Chest X-ray and sputum cytology as well as early operative indication. Although results of these procedures have suggested effectiveness attained by mass screening, standard of efficiency have not been same in all the areas, where the screening having been performed, but there has been difference between respective areas, therefore, in order to make the every result of mass screening carried out in areas similar, it is necessary to make the indication of mass screening being done with careful attention for lung cancer cases.     

痰隐血与胸片筛查肺癌比较研究

目的比较痰隐血与X线胸片筛查肺癌效果。方法2007年1至7月在云南省宣威市来宾镇对35—70岁近3万居民（来宾镇共有人口近9万人）作肺癌首次筛查,第一阶段先作胸部X线拍片,发现肺部阴影可疑者437例,再经CT精查,175例肺内有可疑占位病变,疑诊肺癌,其中30例有手术适应证,自愿接受手术治疗;术后27例病理确诊肺癌,另3例未见癌。4个月后除X线已确诊者外,进入第二阶段痰隐血筛查共25010例,每人发给痰盒一个,早晨深咳痰,做痰隐血检测,不变色为阴性（一）。变蓝色者为阳性,当即在痰变蓝色处用竹签挑痰,涂玻璃片一张,滴纯酒精2～3滴固定标本,送细胞学检查找癌细胞。结果痰隐血阳性共2429例,列为肺癌一级高风险人群,占筛查人群的9．71％（2429／25010）,其中弱阳性（＋）占66．73％（1621／2429）,涂片发现癌细胞9例,癌检出率0．56％（9／1621例）;阳性（＋＋）615例,检出癌7例,癌检出率1．14％（7／615）。强阳性（＋＋＋）194例,检出癌6例,癌检出率3．09％（6／194）。痰隐血量越高肺癌检出率越高;细胞学报告上皮细胞有中度或重度不典型增生者281例,可疑癌或癌者22例,经薄层CT确诊早期肺癌者7例,这些患者先前X线片未见异常。另15例痰癌细胞阳性患者,CT未找到原发病灶,待观察。结论痰隐血与X线胸片筛查肺癌相比的优点：（1）痰隐血比X线胸片可省90％资源;（2）痰检出的肺癌多数是早中期,在胸片上看不到;（3）痰细胞不典型增生率为11．6％,提前5—10年预报癌前病变,警示肺癌高风险,X线胸片无法做到。     

Cancer screening: evidence and practice in Europe 2008

We examine the theoretical basis of screening, followed by an evaluation of screening initiatives from a population health perspective and a discussion of the organisation of mass screening programmes. Evidence for the effectiveness of screening by primary site from both randomised trials and evaluation of service screening is summarised and the existing cancer screening programmes in the European Union are described. Sufficient evidence from several randomised trials to demonstrate mortality reduction exists for breast cancer and colorectal cancer screening. At least one trial has shown efficacy with a mortality end-point in screening for hepatocellular carcinoma and oral cancer. Randomised trials have demonstrated a lack of mortality effect in lung cancer screening based on chest X-ray and sputum cytology. Despite the lack of randomised trials, population screening for cervical cancer with cytological smears has been convincingly shown to reduce cervical cancer incidence and mortality.     

Sensitivity and specificity of lung cancer screening in Osaka, Japan

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981-1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.     

Sensitivity and Specificity of Lung Cancer Screening in Osaka, Japan

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981–1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.     

Molecular sputum analysis for the diagnosis of lung cancer

Lung cancer is the leading cause of cancer mortality rate worldwide, mainly because of the presence of metastatic disease at the time of diagnosis. Early detection of lung cancer improves prognosis, and towards this end, large screening trials in high-risk individuals have been conducted since the past century. Despite all efforts, the need for novel (complementary) lung cancer diagnostic and screening methods still exists. In this review, we focus on the assessment of lung cancer-related biomarkers in sputum in the past decennium. Besides cytology, mutation and microRNA analysis, special attention has been paid to DNA promoter hypermethylation, of which all available literature is summarised without time restriction. A model is proposed to aid in the distinction between diagnostic and risk markers. Research on the use of sputum for non-invasive detection of early-stage lung cancer has brought new insights and advanced molecular techniques. The sputum shows a promising potential for routine diagnostic and possibly screening purposes.     

Cases of head and neck carcinoma detected by sputum cytology--lung cancer screening and head and neck cancer

Seven cases of head and neck carcinoma are presented. They were first noticed by sputum cytology, which was ordered to check lung cancer because of hemosputum (three cases), or in a general check-up of asymptomatic individuals. None of them had lung cancer, and three were found to have piriform sinus carcinoma, two mesopharynx carcinoma, and two vocal cord carcinoma. All seven cases were histologically diagnosed as squamous cell carcinoma. Their clinical stages were as follows; T 1 N 0, three cases; T 1 N 1, one case; T 2 N 0, two cases; T 2 N 1, one case (UICC 1978). These cases remind us that positive sputum cytology is not only a sign of lung cancer, but also of other upper aerodigestive tract malignancies. Sputum cytology may be useful for checking asymptomatic head and neck cancer patients, though it is still too costly and time-consuming to be applied to mass screening.     

The Cell‐CT 3‐dimensional cell imaging technology platform enables the detection of lung cancer using the noninvasive LuCED sputum test

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5‐year survival rate for lung cancer has changed little over the past 40 years. Early detection through emerging lung cancer screening programs promise the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Screening Trial reported that screening using 3 consecutive low‐dose x‐ray computed tomography scans provides a 20% reduction in lung cancer mortality compared with chest x‐ray. However, this reduction in mortality comes with an unacceptable false‐positive rate that increases patient risks and the overall cost of lung cancer screening. The LuCED test for detection of early lung cancer is reviewed in the current article. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell‐CT, which images cells in 3 dimensions with submicron resolution. Algorithms are applied to the 3‐dimensional cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification that could enable the cost‐effective detection of lung cancer. Cancer (Cancer Cytopathol) 2015;123:512–523. © 2015 American Cancer Society.     

Digital mammo-radiography (DMR) in mass screening for breast cancer

There are still many problems to be overcome in the development of mammographic apparatus suitable for mass screening purposes, but a certain number of these have been solved in the system discussed in the present paper. The equipment employs the technique of displaying I.I. images on a monitor by means of an image processor. This possesses the advantages of both film mammography and xeromammography, and the X-ray dose involved is small. The following advantages over film mammography are offered: The system is capable of clearly bringing out very minor differences of contrast. Tumor shadows can be easily displayed. The X-ray dose is small: 0.03-0.05 R. The equipment is inexpensive to use. Patient positioning is simple, and examinations take little time. Long operator training programs are unnecessary. The system uses digital signals, and so automatic diagnosis is possible. Theoretically, at least, tumors as small as 0.2 mm in diameter can be detected. The future goal is discovering unpalpable breast cancers. DMR is useful because of low dose, low cost and high safety. In our study as screening for breast cancer, DMR system shows high sensitivity (87.1%), specificity (78.7%) in 391 cases of out patients.     

Occult lung cancer with positive cytology and normal chest film--an analysis of 54 cases

From 1973 to 1980 and 1982 to 1984, mass annual screening was carried out in Yunnan Tin Corporation. Chest X-ray and sputum cytology were used to detect lung cancer among subjects with an underground work history over 10 years and over 40 years of age. 54 cases of occult lung cancer with positive cytology and negative X-ray plain film were found, 48 out of 100,725 subjects and 6 out ot 8,808 out-patients. 42 lesions were located by bronchoscopy and 12 by various roentgenologic examinations. Among these 54 cases, 52 (96.3%) were central type lung cancers. Squamous cell carcinoma was found in 53 and small cell anaplastic carcinoma in only 1. Diagnosis was established by pathology in 35 and by cytology in 19. In 18 cases treated by surgery, there were 15 Ia stage and 3 Ib (UICC staging system). 3 Ib died of recurrence 33, 62 and 101 months after operation. 1 Ia died of residual cancer recurrence 21 months after sleeve-resection. The overall 5 year survival rate was 91.6% (11/12). The authors believe that X-ray plain films sometimes fail to detect the early stage central type lung cancers. Bronchoscopy, in particular fiberoptic bronchoscopy is one of the most effective means in diagnosis and location. By bronchoscopy, in general, the tumor could be detected and the extent of involvement in the bronchus assessed. Finally, the authors emphasize that mass screening is a useful method to detect early lung cancer among the high risk population.     

Early hilar lung cancer: its clinical aspect

Early hilar lung cancers are rare, but are curable if they are properly diagnosed and treated. In the past 14 years, we have treated 27 patients with early hilar cancers that fulfilled the criteria proposed by the Japanese Lung Cancer Society (JLCS). Eighteen patients presented with symptoms and 9 were detected by the mass screening examination of sputum cytology. All lesions in both groups were finally diagnosed by bronchoscopy. Twenty patients (74%) had positive sputum cytology, whereas only 7 (26%) had positive chest X-ray findings. All the patients underwent surgery, and bronchoplasty was the most frequent operative procedure. The 5-year survival rate was 100%, and the 10-year survival rate was 91.7%, as one patient died of a second primary lung cancer in the 6th postoperative year. In conclusion, the definition of early hilar lung cancer proposed by the JLCS is thought to be reasonable, and early hilar lung cancer is a curable disease, if it is properly diagnosed and treated.     

Bronchoscopic diagnosis of lung cancer in early stage

Early lung cancer has been classified into peripheral and hilar types. The peripheral type early lung cancer is the tumor size of under 2 cm with N0, M0, and many cases are detected with Chest X-ray findings. The bronchofiberscopic curettage is performed for its definitive diagnosis. The hilar type early lung cancer is limited within the bronchial wall, and its X-ray findings are normal in most cases. Usually the detection is made with bloody sputum or sputum cytology, and its definitive diagnosis is obtained with the bronchofiberscopic biopsy under direct visualization. In the case with no irregular endoscopic findings in spite of the positive result in sputum cytology its localization can be obtained with special methods such as selective bronchoalveolar lavage, image processing or laser irradiation.     

Detection of p53 mutations in sputum smears precedes diagnosis of non-small cell lung carcinoma

Little progress has been made in reducing lung cancer mortality by applying conventional methods to early diagnosis and screening. Recent advances in molecular oncology, however, have provided tools which may be of use in this area. p53 gene mutation is the most common gene alteration in the development of lung cancer. Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of lung cancer. In this study, we attempted to establish a polymerase chain reaction (PCR)-based assay for assessing the possibility of early detection of p53 mutation in archival Papanicolaou-stained cytologic sputum smears. Ten sputum smear slides were collected prior to clinical diagnosis from 10 lung cancer patients who had been confirmed to have p53 mutations in surgically resected lung tumors. We successfully obtained sufficient amounts of RNA from each sputum smear specimen for amplification of PCR and direct sequencing. Only one patient was found to have p53 mutation at codon 286; the other nine patients had wild type p53 genes. This result supports the possibility that detection of p53 mutations in cytologic sputum smears is an available strategy for the early diagnosis of lung cancer.     

The influence of lung cancer mass screening on surgical results.

BACKGROUND: After the introduction of the mass screening program for lung cancer, the number of patients detected by mass screening increased as well as the number of early staged patients. Therefore, we examined the influence of lung cancer mass screening on surgical results. METHODS: A total of 1177 primary lung cancer cases, who underwent surgery from 1963 to 1992, were retrospectively reviewed. They were grouped according to the changes in the mass screening system: the first period (1963-1977) before lung cancer screening started, the second period (1978-1986) when mass screening was conducted by the local government, and the third period (1987-1992) after the launching of the national screening program. RESULTS: The rate of cases detected by mass screening increased over time and the 5-year survival rate improved significantly, from 33.7% in the first period, to 51.8% in the second period and finally, to 58.4% in the third period. The improvement is attributable to a relative increase of rate of stage I cases and better stage I survival rate. Specifically, in stage I cases, improvement resulted from a relative increase of stage IA in peripheral type and roentgenographically occult lung cancer cases and from better survival rate of these two groups. CONCLUSION: As lung cancer screening has come into widespread use, detection of peripheral small-sized lung cancer and roentgenographically occult lung cancer have increased and consequently, surgical results have improved.     

肺癌早期诊断研究进展

肺癌是绝大多数国家主要的癌症死亡原因,早期诊断和早期治疗尤为重要.以胸部X光片、螺旋CT、支气管内镜、痰液细胞学等检测手段用于肺癌的筛检和早诊已有较多报道,但鉴于以上检查手段的敏感性、特异性、适用度等方面的局限,近年来国内外学者对有关肺癌早期诊断的分子标志物做了大量有益的探索,本文拟就该领域的相关进展作一综述.     

云南锡矿工肺癌的队列研究

目的；建立矿工肺癌队列，探讨云锡矿工肺癌的危险因素，为肺癌早期标志物研究和肺癌防治研究提供基础。方法：以特殊人群为基础的前瞻性研究，每年用痰检和胸部X线对高危云锡矿工进行肺癌筛查，建立动态队列，分析氡、砷暴露等因素与肺癌的关系，并收集痰脱落细胞、胸片和其它生物样本。结果；1992－1999年间共有9143人进入队列，发现460例肺癌新病例，进行了47655人次胸部X线检查和46625人次痰检，年龄调整慢性支气管炎、硅肺和吸烟暴露RR分别为1．73、1．46和1．32。结论：成功建立了云锡职业暴露队列。作氡、砷暴露是该高危人群肺癌的危险因素外，慢性支气管炎、硅肺和吸烟也与肺癌发病有关。     

Cancer screening in Japan--a critique from the epidemiological viewpoint

The present status of cancer screening in Japan has been critically reviewed from an epidemiological point of view. Cancer screening programs for stomach cancer and uterine cervical cancer were introduced in the 1960s on the basis of the naive belief of many clinicians that early diagnosis is beneficial: Many studies now show that this belief unfounded. Therefore, before the introduction of screening programs as a general policy, epidemiological evaluation is essential. The general principles involved in evaluation of cancer screening were discussed. In contrast to stomach cancer and uterine cervical cancer, cancers of the lung, breast and colorectum are increasing in Japan. In the case of lung cancer, primary prevention, i.e., smoking control, should be preferred, because lung cancer screening has not yet been shown to be effective. In the case of breast cancer and colorectal cancer, screening trials should be designed and appropriate evaluations should be conducted before their implementation as cancer control measures.     

Screening for lung cancer

Lung cancer incidence is increasing. Survivability has increased over the last few years particularly in certain subsets and has also been shown to increase with early detection. Chest X-ray and sputum cytology have been the mainstays of screening programs. Although survival is increased, overall mortality rates seem unchanged except in certain subsets. Whether the addition of serum markers or use of monoclonal antibodies, automated cytological, and computer-aided techniques will show decrease in mortality remains to be documented. We recommend yearly chest X-rays, sputum cytology in high-risk patients, i.e., age greater than 65, greater than 20 year history smoking, other significant carcinogenic exposure. Serum markers, monoclonal antibodies, and advanced, automated cytology methods are yet to be tested and therefore should be considered in clinical trials only.     

Screening for breast cancer in a high-risk series

A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer Institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening.     

Outcome of patients with lung cancer detected via mass screening as compared to those presenting with symptoms.

We performed lung cancer resection in 721 patients between 1980 and 1989. Cancers were detected via mass screening programs by annual chest X-ray examination in the majority of cases. We evaluated the surgical results in patients with tumors detected by mass screening and compared them to those in whom the malignancy was detected by symptoms. Lesions in the mass screened group were T1 to T2 tumors in 90% of the cases, and NO in 73%. Stage I disease accounted for 65.3% in the mass screened group. The overall 5-year survival rate was 56.2% in the mass screened group, which was significantly better than the 25.3% for the symptom group (P less than 0.001). The surgical results in the lung cancer cases detected by the mass screening program had better results than the cases who presented with symptoms.