Category: Sputum lung cancer detection

Sputum lung cancer detection

Introduction: Biomarkers may prove to be valuable tools to manage those at risk of lung cancer.

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Sputum analysis using DNA cytometry has shown promise, but an automated, objective sputum analysis test has yet to be developed.

This study evaluated the performance characteristics of the LungSign test for lung cancer and compared them to conventional cytology. Methods: A multicenter validation trial was conducted in which sputum specimens were prospectively collected from subjects suspected of having lung cancer during diagnostic workup. Specimens were placed on slides, DNA stained using Feulgen thionin, and analyzed using an automated cytometry-based scoring system.

Smears were also prepared from the sputum specimens, stained by the Papanicolaou procedure, and analyzed using conventional cytology. LungSign scores and conventional cytology results were compared with the subject diagnoses.

Results: A total of high-risk subjects were enrolled at nine clinical sites. Test performance was statistically equivalent across cancer stages, histologic types, and localizations for analyzable lung cancer subjects.

sputum lung cancer detection

LungSign receiver operating characteristic area under the curve measure for the test was 0. Conclusions: DNA cytometry of sputum using the LungSign test detects stage I lung cancer and may provide a new tool to manage high-risk individuals. Abstract Introduction: Biomarkers may prove to be valuable tools to manage those at risk of lung cancer.

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This study evaluated the performance characteristics of the LungSign test for lung cancer and compared them to conventional cytology Methods: A multicenter validation trial was conducted in which sputum specimens were prospectively collected from subjects suspected of having lung cancer during diagnostic workup. Gov't Validation Study.Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate.

Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung.

sputum lung cancer detection

Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.

The low survival rate of NSCLC patients is related to the late presentation of patients with an unresectable tumor due to the lack of a validated screening approach for early detection. By early detection of precancerous microscopic lesion, patients can avoid developing clinically diagnosable cancer and high-risk healthy individuals can be prevented from developing cancer by timely chemoprevention. Therefore, early detection of lung cancer, followed by appropriate treatment, will significantly increase the survival rate.

Low-dose computerized tomography CT scan has suggested a promising possibility to detect lung cancer earlier. Compared to chest X-rays, CT screening significantly reduced mortality in a high-risk population by Although it is promising, the limited impact of CT screening on mortality may be because it cannot distinguish non-calcified nodules NCNs that progress to cancer from the benign ones. It also has limited ability to differentiate between benign and malignant lesions of tumors, especially the centrally located ones [ 3 ], demanding a complementary screening tool to increase specificity of detection for cancer.

False-positive CT screening results will lead to unnecessary invasive procedures, which can cause stress and economic burden. Therefore, there is still a demand for non-invasive, sensitive biomarkers in order to accurately identify the high-risk population for optimal treatments and minimize unnecessary invasive procedures caused by false-positive CT screening results. These biomarkers will be also useful to increase sensitivity for the detection of centrally located lung cancer and to determine the strategy for the therapeutic management of clinically uncertain nodules that are detected by CT screen.

Tobacco smoking is the single, most important risk factor for lung cancer. It is well accepted that the repeated exposure of the respiratory tracts of smokers to tobacco-related carcinogens causes molecular genetic and epigenetic abnormalities that culminate in lung cancer. Consequently, smoking may create a field of molecular injury throughout the airway epithelium exposed to cigarette smoke and increase the susceptibility of an entire field or area to carcinogenesis field carcinogenesis [ 5 ].

This suggests that the smoke-induced molecular abnormalities found in the respiratory tract regardless of its exact location may mirror the progression of cancer and therefore can be used as potential biomarkers to detect lung tumor at an early stage. Thus, sputum that contains exfoliated airway epithelial cells is an ideal specimen type for the discovery of biomarkers for lung cancer.

Molecular analysis of sputum has been an active area for the investigation of lung cancer biomarkers for several reasons. Sputum is the most easily accessible body fluid that contains the pathogenically relevant cell type, namely, bronchial epithelial cells.

These cells are typically exfoliated from the central airways, where the CT scan seems to have a blind spot when the cancer arises from here. This also suggests that it is possible to identify tumor cells in sputum. Additionally, the other airway epithelial cells found in sputum may also harbor important molecular information, supported by the field cancerization theory [ 5 ], which reflects the local milieu of the lung. High-risk smokers typically produce increased amount of sputum, which makes it feasible to obtain enough material for analysis.

Finally, collecting sputum is non-invasive, fast, and economical, which are important characteristics to be an ideal specimen type for large-scale population screening. In this review, we discuss various sputum-based molecular biomarkers and how each one has developed during the last decade. We then explore the strengths and weaknesses of each marker and discuss ways to overcome the limitations.

Sputum cytology is the oldest technique that utilizes sputum in detecting lung diseases.Lung cancer is the leading cause of cancer-related deaths over the world, characterized by a very high mortality rate.

Detection of lung cancer by automated sputum cytometry

Molecular technique development tries to focus on early detection of cancers by studying molecular alterations that characterize cancer cells. Worldwide lung cancer research has focused on an ever-increasing number of molecular elements of carcinogenesis at genetic, epigenetic and protein levels.

The non-invasiveness is the characteristic that all clinical trials on cancer detection should have.

sputum lung cancer detection

Since smokers have higher quantity of sputum containing exfoliated cells from the bronchial tree, and the sputum represents the most easily accessible biological fluid and its collection is non-invasive, analysis of this sample represents a good area of research in early lung cancer diagnosis. A large prospective trial of almost half a million non-smokers showed as lung cancer is also common in patients with COPD who have never smoked.

This review describes issues related to early lung cancer screening using non-invasive methods. Abstract Lung cancer is the leading cause of cancer-related deaths over the world, characterized by a very high mortality rate.

Publication types Review.Sputum, or phlegm, is the fluid that is secreted by cells in the lower respiratory tract such as the bronchi and the trachea. It differs from saliva, in that it contains cells that line the respiratory passages. If your doctor has recommended a sputum cytology, what this entails and how the sample is taken. There are a number of reasons why a doctor might order a sputum cytology test.

Some of these include:. Sputum cytology may be done to diagnose a wide array of conditions including:. Sputum cytology, at least at the current time, is not a good test for screening for lung cancer. The test is more accurate in diagnosing squamous cell carcinoma of the lungs than lung adenocarcinoma. Sputum cytology also lacks the ability to determine the location of the cancer or to accurately determine the subtype of lung cancer histology present, so further tests will be needed.

Eosinophils are a type of white blood cells that are present in increased amounts with allergies. Studies suggest that determining sputum eosinophils is useful when combined with symptoms to tailor the treatment of asthma and reduce the number of asthma exacerbations.

A special type of sputum cytology may be done to diagnose tuberculosis. In this procedure, a pathologist may see bacteria. Based on the particular shapes of the bacteria whether they look round or like rods, and what they look like with different stains, your doctor can choose the best antibiotic for beginning treatment.

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A sputum cytology can narrow down the choices of a correct antibiotic or combinations of antibiotics considerably. Like any medical test, there can be risks associated with a sputum cytology exam, but the most important "risk" is that the test will miss what it is looking for. Since the test requires people to "cough up" sputum, it may be uncomfortable and can stimulate coughing "jags" for people with lung disease.

Before you have a sputum cytology test your doctor will explain what the procedure entails and discuss what she expects she may find. She will ask you about your symptoms leading to the test, as well as prior medical conditions and any family history of lung diseases or lung cancer.

The test itself takes only a few minutes, but it's important to allow time to talk to your doctor if it will be done as part of an appointment or answer any questions the technician will have if it is done at a lab-only appointment. A sputum cytology is often done at your clinic but can be done at a hospital lab as well. Since you will be asked to take some deep breaths and bring up sputum, you should wear comfortable clothing and clothing that can easily be washed if some of the sputum should drip onto your clothing.

Most people are able to complete their sputum cytology test in the exam room where they see their doctor, or in an adjacent lab suite. Before you have your sputum cytology sample taken, your doctor or nurse will give you special instructions to follow. On the day of the procedure, you will want to carefully rinse your mouth and teeth, but it's important to not use toothpaste.

You will want to blow your nose prior to the procedure to minimize the amount of upper airway drainage you have. During your test, you will be asked to forcefully cough into a container. A sputum cytology may also be done during a bronchoscopyand will vary somewhat. When you are doing the procedure, the nurse will help you take deep breaths and expectorate from deep in your chest.

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It will be important to bring up fluids as if you are coughing rather than spitting. People often have to attempt getting a sample more than once, as it can be difficult obtaining sputum instead of saliva. Once the sputum sample is obtained, it is looked at under the microscope.

Special stains may be done, and other techniques to further define what is being seen.

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If bacteria are present, the sample will then be placed in a culture and grown a sputum culture to determine exactly which bacteria are causing an infection. While this procedure has not been found to be an effective screening test for lung cancerwhen done on someone with symptoms, it can sometimes result in a diagnosis of lung cancer. Even though it was found that sputum cytology is not adequate as a screening test, studies are ongoing looking to see what possible role it may have in the diagnosis of lung cancer.

In recent years, the most common types of lung cancer have changed. These cancers tend to grow near the large airways. Now the most common type of lung cancer is lung adenocarcinoma.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.

sputum lung cancer detection

The sputum shows a promising potential for routine diagnostic and possibly screening purposes. Abstract Lung cancer is the leading cause of cancer mortality rate worldwide, mainly because of the presence of metastatic disease at the time of diagnosis.

Publication types Research Support, Non-U. Gov't Review. Substances Biomarkers, Tumor.Anderson Cancer Center, Houston, Texas. Sputum is an easily accessible diagnostic material for lung cancer early detection by cytologic and molecular genetic analysis of exfoliated airway epithelial cells.

We propose to obtain concentrated and purified bronchial epithelial cells to improve early detection of lung cancer in sputum samples. Sputum was collected from patients with stage I nonsmall-cell lung cancer, cancer-free smokers, and healthy nonsmokers. Magnetic-assisted cell sorting MACS with anti-CD14 and anti-CD16 antibody beads were used to enrich bronchial epithelial cells by depleting macrophages and neutrophils from sputum.

Sputum analysis: non-invasive early lung cancer detection

Furthermore, only 2 cytocentrifuge slides of the unenriched sputum were needed for the analyses, as compared with up to 10 cytocentrifuge slides required from the unprocessed specimens. The enrichment of bronchial epithelial cells could improve the diagnostic value of sputum and the efficiency of genetic and cytologic analysis of lung cancer. Nonsmall-cell lung cancer NSCLCmainly comprising adenocarcinomas and squamous cell carcinomas of lung, is the number 1 cancer killer in the US and worldwide.

Chest X-ray has been used for the early detection of lung cancer; however, the sensitivity is low. Thus, the development of sensitive and noninvasive approaches for the early diagnosis of lung cancer is clearly important to reduce mortality.

Because sputum is 1 of the most easily accessible materials and contains exfoliated airway epithelial cells from the bronchial tree, it has been considered a suitable diagnostic material for assessing carcinogenic damage in lung tumors. Furthermore, there is a dramatic variation in intra- and interobserver agreement in determining cancer cells because of the uncertainties of pattern recognition and classification by cytopathologists. Instead of observing morphologic characterization by cytology, molecular genetic study of sputum could identify the cells containing tumor-related genetic aberrations, which occur in microscopically normal-appearing epithelium and are specific signs of the progression of tumorigenesis.

Magnetic cell sorting MACS is a process of immunomagnetic cell selection based on the recognition of cell-specific antibodies coupled to magnetic beads. The objective of the study was to obtain concentrated and purified bronchial epithelial cells from sputum to improve diagnosis of lung cancer in sputum samples. Written informed consent for participation was obtained through an Institutional Review Board-approved protocol.

Sputum was collected by the method described by Pizzichini et al. Subjects were asked to blow their nose, rinse their mouth, and swallow water to minimize contamination of squamous cells from postnasal drip and saliva. Sputum samples were then coughed in a sterile container and processed within 2 hours.

Molecular sputum analysis for the diagnosis of lung cancer

To further minimize oral squamous cell contamination, opaque or dense portions that looked different from saliva under the inverted microscope were selected using blunt forceps from expectorate. The samples were processed on ice in 4 volumes of 0.

Absolute cell numbers and cell viability were quantitated by using a hemacytometer with trypan blue. Two cytocentrifuge slides equivalent to cells per slide were prepared from aliquots of cell suspension by using a cytospin machine Shandon, Pittsburgh, Pa and were then stained with the Papanicolaou staining technique.

An enrichment column Miltenyi Biotech with a diameter of 1. The incubated cells were fed into the column and the flow-through eluate was collected in a 10 mL sterile tube on ice.

The eluate was centrifuged at g for 10 minutes.

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At least 8 cytocentrifuge slides were made from each enriched sample in single preparations by using a cytospin machine Shandon. Similarly, 20 cytocentrifuge slides were prepared from each unenriched sample by using a cytospin machine Shandon. Ten of the slides were stained with the Papanicolaou staining technique for cytologic diagnosis. The rest of the cytocentrifuge slides were fixed in the methanol and glacial acetic acid solution for the FISH analysis. Cytologic diagnosis of the Papanicolaou-stained slides was performed by 2 senior cytopathologists using the classification of Saccomanno et al.The default is to predict NA.

This can be a numeric vector or a one-sided model formula. In the latter case, it is interpreted as an expression evaluated in newdata. If the logical se.

Early Detection of Lung Cancer: What you need to know.

If the numeric argument scale is set (with optional df), it is used as the residual standard deviation in the computation of the standard errors, otherwise this is extracted from the model fit. Setting intervals specifies computation of confidence or prediction (tolerance) intervals at the specified level, sometimes referred to as narrow vs.

If the fit is rank-deficient, some of the columns of the design matrix will have been dropped. Prediction from such a fit only makes sense if newdata is contained in the same subspace as the original data. That cannot be checked accurately, so a warning is issued. If newdata is omitted the predictions are based on the data used for the fit. In that case how cases with missing values in the original fit are handled is determined by the na.

The prediction intervals are for a single observation at each case in newdata (or by default, the data used for the fit) with error variance(s) pred. This can be a multiple of res. If weights is supplied, the inverse of this is used as a scale factor. For a weighted fit, if the prediction is for the original data frame, weights defaults to the weights used for the model fit, with a warning since it might not be the intended result.

If the fit was weighted and newdata is given, the default is to assume constant prediction variance, with a warning. Variables are first looked for in newdata and then searched for in the usual way (which will include the environment of the formula used in the fit). A warning will be given if the variables found are not of the same length as those in newdata if it was supplied.

Notice that prediction variances and prediction intervals always refer to future observations, possibly corresponding to the same predictors as used for the fit. The variance of the residuals will be smaller.

Strictly speaking, the formula used for prediction limits assumes that the degrees of freedom for the fit are the same as those for the residual variance. This may not be the case if res. SafePrediction for prediction from (univariable) polynomial and spline fits.

An optional data frame in which to look for variables with which to predict.


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