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Pathology and genetics of tumours of the lung , pleura, thymus and heart

The American Society of Clinical Oncology (ASCO) previously published evidencebased guidelines for the treatment of unresectable non–small-cell lung cancer (NSCLC) [1]. ASCO guidelines are updated periodically by the responsible Expert Panel (Appendix) [2]. For the 2003 update, a methodology similar to that applied in the original ASCO practice guidelines for treatment of unresectable NSCLC was used. Pertinent information published from 1996 through March 2003 was reviewed. The MEDLINE database (1996 through October 2002; National Library of Medicine, Bethesda, MD) was searched to identify relevant information from the published literature for this update. A series of searches was conducted using the medical subject headings, “carcinoma, non–small-cell lung,” “diagnostic imaging,” “neoplasm staging,” “mediastinoscopy,” “bone neoplasms,” “brain neoplasms,” “liver neoplasms,” “adrenal gland neoplasms,” “non–small-cell lung cancer,” “radionuclide imaging,” “bisphosphonates,” “radiotherapy,” “smoking,” “chemoprevention,” and the text words “chemotherapy,” “bone scan,” “PET,” and “zoledronic acid.” These terms were combined with the study design–related subject headings or text words “meta-analysis” and “randomized controlled trial.” Search results were limited to human studies and English-language articles. The Cochrane Library was searched in October 2002 using the phrase “lung cancer.” Directed searches based on the bibliographies of primary articles were also performed. Randomized trials published in the literature since October 2002, as well as data presented at ASCO Annual Meetings, were added to the evidence for these guidelines at the discretion of members of the Expert Panel. The entire update committee met once to discuss strategy and assign responsibilities for the update. A writing committee subsequently met to further review the literature searches, collate different sections of the update, and refine the manuscript. A draft update was circulated to the full Expert Panel for review and approval. The final document was also reviewed by ASCO’s Health Services Research Committee and the ASCO Board of Directors. Each recommendation from the 1997 guideline is listed below, and is followed by an updated (2003) recommendation, if applicable. “No change” is indicated if a particular recommendation has not been revised. A summary of the evidence follows thereafter. In order to preserve the framework of the 1997 guideline, information and recommendations regarding major topics, such as fluorodeoxyglucose positron emission tomography (FDGPET), have been divided and distributed to the appropriate section of the text. ASCO considers adherence to these guidelines to be voluntary. The ultimate determination regarding their application is to be made by the physician in light of each From the American Society of Clinical Oncology, Alexandria, VA.

https://ascopubs.org/doi/pdf/10.1200/JCO.2004.09.053

American Society of Clinical Oncology Treatment of Unresectable Non–Small-Cell Lung Cancer Guideline: Update 2003

Context Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. Objective To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. Data Sources MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). Study Selection Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. Data Extraction Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. Results Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53 454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 247 vs 309 events per 100 000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. Conclusion Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

/pdf/benefits-and-harms-of-ct-screening-for-lung-cancer-a-2aq08gzpoz.pdf

Benefits and Harms of CT Screening for Lung Cancer: A Systematic Review

The present invention provides systems, methods, screens, reagents and kits for optical system analysis of cells to rapidly determine the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for those that specifically affect particular biological functions.

A system for cell-based screening

Lung cancer is the leading cause of death from cancer among men and women in the United States. More people die each year of lung cancer than of colon, breast, and prostate cancer combined. Despite new diagnostic techniques, the overall five-year survival rates remain about 14 percent, and most patients still present with advanced disease.1 There has long been interest in screening to detect lung cancers when they are smaller and presumably at earlier and more curable stages, as witnessed by the support for previous screening trials using chest radiography and cytologic examination of sputum. Unfortunately, these studies failed to . . .

Screening for lung cancer.

A system and method for detecting diagnostic cells and cells having malignancy-associated changes are disclosed. The system includes an automated classifier having a microscope, camera, image digitizer, a computer system for controlling and interfacing these components, a primary classifier for initial cell classification, and a secondary classifier for subsequent cell classification. The method utilizes the automated classifier to automatically detect diagnostic cells and cells having malignancy-associated changes. The system and method are particularly useful for detecting these cells in cell samples obtained from bronchial specimens such as lung sputum.

System and method for automatically detecting malignant cells and cells having malignancy-associated changes

A method for detecting malignancy-associated changes. A sample of cells is obtained and stained to identify the nuclear DNA material. The sample is imaged with a digital microscope. Objects of interest are identified in the sample of cells based on the intensity of the pixels that comprise the object versus the average intensity of all pixels in the slide image. An exact edge is located for each object and variations in the illumination intensity of the microscope are compensated for. A computer system calculates feature values for each object and, based on the value of the features, a determination is made whether the cell exhibits malignancy-associated changes or not.

Method and apparatus for automatically detecting malignancy-associated changes

Objective: To investigate the hypothesis that image cytometry of sputum specimens can detect squamous carcinoma without requiring visually abnormal cells. Design: The sensitivity and specificity of image cytometry were evaluated in a case-control study. Material and Methods: Seventy-three sputum slides from the Mayo portion of the National Cancer Institute Cooperative Early Lung Cancer Study were restained by a modified Feulgen method. We examined 40 slides from 9 patients in whom squamous carcinoma developed and 33 slides from 11 patients in whom no cancer developed during a follow-up of at least 5 years. Images of normal epithelial nuclei were collected by using an automated image cytometer. Discriminant analysis was used to determine differences in DNA distribution of normal nuclei in sputum specimens from noncancer patients versus normal nu-clei in sputum samples from patients in whom carcinoma developed. Results: By using features based on DNA distribution, 74% correct classification of nuclei was possible without human review of the material and without the use of visually abnormal nuclei. A receiver operating characteristic curve demonstrated sensitivities and specificities, including 40% sensitivity and 90% specificity. Conclusion: Although this study was limited to 20-year-old slides and squamous cell carcinoma, automated image cytometry detected a substantial proportion of patients with squamous cell cancer without using visually abnormal nuclei.

https://www.mayoclinicproceedings.org/article/S0025-6196(11)63587-8/pdf

Sputum Screening by Quantitative Microscopy A Reexamination of a Portion of the National Cancer Institute Cooperative Early Lung Cancer Study

Muon level-crossing spectroscopy of organic free radicals

Bimolecular rate constants for the thermal chemical reactions of muonium (Mu) with hydrogen and deuterium—Mu+H2→MuH+H and Mu+D2→MuD+D—over the temperature range 473–843 K are reported. The Arrhenius parameters and 1σ uncertainties for the H2 reaction are log A (cm3 molecule−1 s−1)=−9.605±0.074 and Ea =13.29±0.22 kcal mol−1, while for D2 the values are −9.67±0.12 and 14.73±0.40, respectively. These results are significantly more precise than those reported earlier by Garner et al. For the Mu reaction with H2 our results are in excellent agreement with the 3D quantum mechanical calculations of Schatz on the Liu–Siegbahn–Truhlar–Horowitz potential surface, but the data for both reactions compare less favorably with variational transition‐state theory, particularly at the lower temperatures.

/pdf/experimental-tests-of-reaction-rate-theory-mu-h2-and-mu-d2-3u01ta17qp.pdf

David M. Garner

Papers

System and method for automatically detecting malignant cells and cells having malignancy-associated changes

Method and apparatus for automatically detecting malignancy-associated changes

Sputum Screening by Quantitative Microscopy A Reexamination of a Portion of the National Cancer Institute Cooperative Early Lung Cancer Study

Muon level-crossing spectroscopy of organic free radicals

Experimental tests of reaction rate theory: Mu+H2 and Mu+D2