Jerome M. Reich

Quantification and consequences of lung cancer CT overdiagnosis

The term “overdiagnosis” designates screen-identification of ancers which would otherwise have remained inevident within he individual’s lifetime. The authors of the current U.S. Prevenive Services Task Force guideline cite a CT-lung cancer screening verdiagnosis estimate of 10–12% (vs. CXR-screened controls) [1]. he chest radiographic (CXR) screening estimate, based on the diferential case number identified by CXR vs. null screening is 25% 2]. As many of the CXR trial control cases, considered as clinially relevant, were equally susceptible to overdiagnosis because hey were identified by an incidental or a trial-prescribed CXR, 25% ay be considered a conservative estimate. The Task Force did not etail their estimate methodology, but the 10–12% range brackets he 11% differential in the number of cases identified in the 6.5ear National Lung Screening Trial (NLST) in the CT screened (1060) s. the CXR screened control group (941) [3]. Net overdiagnosis is he sum of CT (vs. CXR) overdiagnosis, 11% + CXR (vs. null screen) verdiagnosis, 25% = 36%. Because this range excludes control group

Lung cancer growth dynamics

Mathematical modeling furnishes valuable and otherwise unattainable insights, some counterintuitive, into the natural history of lung cancer. We modeled lung cancer growth dynamics to show that: (1) early diagnosis of lethal lung cancer by means of radiographic or CT screening is an unattainable goal. (2) At a given dimension and constant tumor volume doubling time, the rate of diameter increase is an exponential function (base 1.26) of the number of tumor volume doublings, and the rate of increase in volume, a quadratic function of the radius. (3) This methodology delineates the magnitude of diameter increase in small nodules required to discern volume growth. (4) Under the assumption of a high degree of compliance with sequential screens in large-scale trials, mean tumor volume doubling time can be estimated from the prevalence:incidence ratio. For example, in the Mayo Clinic computerized tomography trial, stage IA tumor volume doubling time was 230 days.

Concurrent sarcoidosis and lung cancer.

2009;136;943 Chest Jerome M. Reich Concurrent Sarcoidosis and Lung Cancer http://chestjournal.chestpubs.org/content/136/3/943.1.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2009by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest

Diminished Disease-Free Survival After Lobectomy: Screening Implications

BACKGROUND The aim of this study was to estimate the effect of lobectomy on life expectancy in healthy smokers and consider the implications for lung cancer screening. MATERIALS AND METHODS In a retrospective cohort study that provided a minimum of 15 years of follow-up, we analyzed lung cancer survival, all-cause survival, and fatality (1-survival) of 261 persons with stage I non-small-cell lung cancer who underwent lobectomy at Portland Providence Medical Center between 1978 and 1994. We: (1) compared 5-year disease-free fatality (non-lung-cancer fatality) with lung cancer fatality; and (2) based on actuarial data that demonstrated life expectancy equivalence of the healthiest smokers (whom we assumed would be comparable with subjects judged eligible for lobectomy) in the US population, we compared their long-term, disease-free survival (our primary end point) with actuarial expectations by computing the Kaplan-Meier survival function of the differences between lifetimes since surgery in disease-free persons versus matched, expected remaining lifetimes in the US population. RESULTS (1) Five-year disease-free fatality (16.1%) was 58% as high as 5-year lung cancer fatality (27.6%); (2) disease-free survival was reduced by 6.9-years (95% confidence interval, 5.5-8.3), 41% of actuarial life expectancy (17 years). The divergence from expected survival took place largely after 6 years of follow-up. CONCLUSION Lobectomy materially diminishes long-term disease-free survival in the healthiest smokers--persons judged healthy enough to tolerate major surgery and to have sufficient pulmonary reserve to sustain loss of one-fifth of their lung tissue. In screened populations, diminished survival in overdiagnosed persons will offset, to an undetermined extent, the mortality benefit imparted by preemption of advanced lung cancer.

Mortality vs Case Fatality in the Assessment of Sarcoidosis Lethality

In this issue of CHEST (see page 438), the statement by Mirsaeidi and colleagues 1 that “Th e age adjusted mortality rate for African Americans was 12 times higher than for Caucasians” may lead one to mistakenly infer a far greater lethality in African Americans (AA) than Caucasians (CA). Assuming equal case fatality, mortality will refl ect the incidence ratio; AA to CA 5 12-13:1. 2 Multiple series have shown no AA to CA case fatality diff erence. In a New York City health clinic in which 79% of patients with intrathoracic sarcoidosis were AA, they constituted 66% of those experiencing an adverse course. 3 Unadjusted for incidence, mortality rates can lead to absurd conclusions (eg, sickle cell disease is more and Tay Sachs disease less severe in AA than CA).

Diminished Susceptibility of African-Americans to Non-tuberculous Mycobacterial Disease

The incidence of three granulomatous response diseases—sarcoidosis, tuberculosis, and non-tuberculous mycobacterial pulmonary disease—differ markedly in African–Americans versus Caucasians. In reviewing a large compendium of non-cystic-fibrosis bronchiectasis, we noted that complicating infection with non-tuberculous mycobacteria was relatively infrequent among individuals of African–American descent, confirming previous observations of their inherent resistance. Disease-specific variance among African–Americans in the efficacy of their granulomatous response suggests a nexus, a mediating, immunological mechanism. Environmentally conditioned selection of SLC11A1 (Nramp1) alleles may account for this ethnic variance.

In Defense of Lady Windermere Syndrome

Defense of Lady Windermere Syndrome (LWS) provides a critical analysis of its proposed pathogenesis, evidence supporting a causal role of volitional cough suppression, pathogenesis of M. avium complex (MAC) superimposition, a defense of the eponym, and cites a possible contribution of LWS to the bronchiectasis population.

Erratum to inequivalence of non-aggressiveness in clinically diagnosed lung cancers and overdiagnosis in lung cancer screening trials

Overdiagnosis (OD) designates the screen-identification of cancers which would not have become manifest within the lifetime of an individual due to some combination of indolent growth, immunological editing, limited metastatic potential, loss of vascular supply, and competing lethal morbidities.

Five reasons for caution in advocating low-dose computerized tomographic lung cancer screening

The 53.5K-person, low-dose computerized tomographic (LDCT), National Lung Cancer Screening Trial (NLST) achieved a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality at 6.5-year median follow-up. Failure of European LDCT trials employing null (i.e., unscreened) controls to reproduce this benefit compels caution in adopting a policy of population screening. Additional concerns merit attention: surgical mortality is not trivial; overdiagnosis is substantial; disease-free life expectancy and quality of life are markedly diminished by loss of pulmonary reserve; the combination of overdiagnosis and diminished disease-free life expectancy is pernicious.

Genesis of the Nodular Bronchiectasis Phenotype of Pulmonary Disease Due to Nontuberculous Mycobacteria

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