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Biomedical subjects

Alberto M Marchevsky

Publications and source records attributed to Alberto M Marchevsky.

At least 19 recordsLinked to original sources
PubMed2006

Mesothelioma in patients with nonoccupational asbestos exposure. An evidence-based approach to causation assessment.

The specific parameters of nonoccupational asbestos exposures (NOAE) that can distinguish an idiopathic from an asbestos-caused malignant mesothelioma (MM) are controversial. A systematic literature review yielded 1028 cases with this putative association. Only 287 of those reports had a defined single exposure to a household, building occupant, or neighborhood/community asbestos source. The available "evidence" was used to develop semiarbitrary evidence-based causation guideline rules for the assessment of putative associations between MM and NOAE. The rules are classified into class A (tissue burden analysis shows asbestos body counts or fiber counts in lung tissues comparable to MM caused by occupational exposure to asbestos) and classes B to D based on whether certain combinations of NOAE features and MM (evidence) have been described in over 15% (class B), 5% to 15% (class C), and less than 5% (class D) of the patients reviewed. The proposed 4 classes of evidence-based causation guidelines provide a semiarbitrary framework to evaluate the causation of individual MM patients by NOAE based on decreasing levels of currently available evidence. The neoplasms in classes A to C patients are probably caused by NOAE, with decreasing weight of evidence in the 3 groups. There is minimal evidence to support the causation of MM by NOAE in class D patients. There is no evidence or only anecdotal evidence to support a causal association between MM and NOAE in individuals who cannot be classified into any of the 4 classes. Future studies are needed to provide more comprehensive data regarding the association between MM and NOAE.

Asbestos↗
PubMed2006

Problems in pathologic staging of lung cancer.

CONTEXT: Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy. OBJECTIVE: To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms. DATA SOURCES: Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and intrapulmonary metastasis of non-small cell carcinoma of the lung (pT4 or pM1 according to their location); and the role of the recent American Joint Committee on Cancer terminology for the classification of lymph nodes (isolated tumor cells, micrometastases, and metastases). CONCLUSIONS: The variety of practical problems that can arise during the assessment of important prognostic and predictive features such as resection margin status and evaluation of lymphovascular invasion are reviewed. A brief discussion of the assessment of the effects of neoadjuvant therapy on resected lung neoplasms is also included.

Humans↗
PubMed2006

The use of virtual microscopy for proficiency testing in gynecologic cytopathology: a feasibility study using ScanScope.

CONTEXT: ScanScope software can digitize entire cytology slides. OBJECTIVE: To test the feasibility of using virtual microscopy methods and "virtual Papanicolaou tests" for proficiency testing (PT) in gynecologic cytopathology. DESIGN: Two PT exercises were conducted using virtual microscopy. Five cytopathologists and 1 cytotechnologist interpreted images using 2 different schema as follows: (1) the College of American Pathologists graded diagnostic codes (CAP-GDCs) and (2) the Center for Medicare and Medicaid Services test scoring categories (CMS-TSCs). The number of diagnostic errors using the CAP-GDCs and the CMS-TSCs, the mean length of time spent diagnosing each case, and the impressions by the users regarding the facility of the technology and image quality were studied. RESULTS: In the first PT exercise, the participants provided incorrect diagnoses in 4 to 8 of the 10 test cases using the CAP-GDCs and in 1 to 4 of the 10 test cases using the CMS-TSCs. In the second PT exercise, the number of errors decreased to 1 to 6 using the CAP-GDCs and to 0 to 6 using the CMS-TSCs. The results did not achieve statistical significance. The mean time of 9.4 minutes spent per case in the second PT exercise was significantly shorter than the 14.4 minutes spent per case in the first PT exercise (P < .001). The ease of use of the software and the image quality were scored by all participants as 3+ or as 4+. CONCLUSIONS: This preliminary study shows that virtual microscopy and virtual Papanicolaou tests prepared using ScanScope may provide effective tools for PT. Technical issues that require further investigation are discussed.

Diagnostic Errors↗
PubMed2005

Evidence-based medicine in pathology: an introduction.

Evidence-based medicine (EBM) is a school of thought that has spread rapidly through medicine in the past 2 decades and is eliciting an increasing interest in Anatomic Pathology and Laboratory Medicine. It has been defined as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients." The environmental factors that created a need for EBM and basic concepts of this discipline are reviewed. Methods for the accrual and critical appraisal of the validity of available evidence and its impact, applicability and usefulness in pathology practice are discussed. Basic concepts of bayesian data analysis with an emphasis on concepts such as prior and posterior probability and the use of "holdout" or "test" data are introduced. The future of EBM in pathology is discussed and potential applications of these concepts to pathology practice and research are proposed.

Clinical Laboratory Techniques↗
PubMed2005

The application of special technologies in diagnostic anatomic pathology: is it consistent with the principles of evidence-based medicine?

Proponents of evidence-based medicine (EBM) have emphasized the need to consider the quality of different sources of medical information and have proposed various methods to integrate available "best evidence" into rules, guidelines and other diagnostic, therapeutic and prognostic models. The various factors that can affect the internal validity of studies in anatomic pathology, such as interobserver variability, use of retrospective rather than prospective data and others, are reviewed. The need for testing for the external validity of the results of anatomic pathology studies is introduced, using "test sets" of cases that have not been used to generate the classification or prognostic models. This methodology has been seldom used in anatomic pathology to validate the generalizability of various "entities," usefulness of diagnostic tests under different conditions and other information. Basic concepts of meta-analysis for research synthesis are introduced; these methods have been seldom used in anatomic pathology to integrate information from different studies using quantitative techniques rather than summary tables that merely list the results of various publications. The potential use of decision analysis and value of information analysis for the adoption of new tests is briefly discussed.

Data Interpretation, Statistical↗
PubMed2005

Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a case report and review of the literature.

Swyer-James (MacLeod) syndrome is an acquired form of unilateral hyperlucency of the lung and is characterized by the development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. It may develop as a complication of repeated episodes of pulmonary infection resulting in bronchiolitis obliterans and obstruction of small airways. Most patients with Swyer-James (MacLeod) syndrome can be managed clinically, and the pathologic features of the syndrome have been described in only a few reports. Placental transmogrification of the lung is a rare histopathologic finding that has been described in patients with severe emphysema associated with cigarette smoking, congenital bullous emphysema, and fibrochondromatous hamartomas of the lung and is characterized by the development of peculiar structures in the pulmonary parenchyma that resemble placental villi. To our knowledge, placental transmogrification of the lung has not been previously described in patients with Swyer-James (MacLeod) syndrome. We encountered a 32-year-old man with a history of childhood asthma who presented with progressively severe exertional dyspnea and had unilateral right lung hyperlucency. The patient underwent a right pneumonectomy. Examination of the lung revealed severe mixed centriacinar-panacinar emphysema in all lobes, bullous emphysema in the upper lobe, bronchiectases, mild interstitial pneumonia with fibrosis, and placental transmogrification of the pulmonary parenchyma of all 3 lobes. Here, we review the pathology of Swyer-James (MacLeod) syndrome and the possible pathogenesis of villous-like changes in the lung tissues.

Adult↗
PubMed2005

Do cancer cells selectively mutate HFE to increase their intracellular iron?

Malignant cells compared to their normal counter-parts, have an increased requirement for iron in order to achieve an enhanced cell growth. Transferrin receptor (TfR), an essential transport protein that enables cells to satisfy their need of iron, is upregulated in cancer cells. The hemochromatosis gene (HFE) produces a protein that interacts with TfR; and we hypothesized that tumor cells would selectively mutate HFE to improve their iron-uptake and thus provide themselves a growth advantage over non-tumor cells. A total of 36 non-small cell lung cancer (NSCLC) samples and matched tumor-free tissue from the same individuals were examined for HFE mutations using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Sequencing analysis of the shifted bands in three of 36 cases (in both, the tumor and matching normal tissue of the same individuals) revealed the cysteine to tyrosine substitution at amino acid residue 282 (C282Y) in the protein. Surprisingly, matching samples from one patient with a heterozygous C282Y mutation in the germline, showed loss of heterozygosity in the tumor sample at the mutant HFE allele resulting in loss of the C282Y and retention of the normal allele. In addition, we examined 45 tumor cell lines from 11 different tissues. Five cell lines had a heterozygous mutation of HFE, none had a homozygous HFE mutation in the coding region. In summary, our experiments suggest that HFE mutations are not associated with a growth advantage for cancer cells.

Base Sequence↗
PubMed2004

Frozen section diagnoses of small pulmonary nodules: accuracy and clinical implications.

BACKGROUND: Pulmonary nodules are frequently first diagnosed by frozen section, immediately followed by lobectomy or other procedures. The frozen section diagnosis of pulmonary nodules can be difficult, as inflammatory and fibrotic lesions can be confused for malignancy, creating intraoperative dilemmas for pathologists and thoracic surgeons. METHODS: We reviewed our experience at Cedars-Sinai Medical Center with the frozen section diagnoses of 183 consecutive pulmonary nodules smaller than 1.5 cm in diameter and calculated the sensitivity, specificity, and predictive values of this diagnostic procedure. RESULTS: One hundred and seventy four nodules were correctly classified by frozen section as neoplastic or nonneoplastic, six lesions were diagnosed equivocally, and two neoplasms were missed owing to sampling errors. The equivocal frozen section diagnoses included two bronchioloalveolar carcinomas (BAC) interpreted as "atypical hyperplasia, favor BAC," two BAC diagnosed as "alveolar hyperplasia," and two carcinoid tumors labeled as "atypical carcinoma" and "spindle cell lesion, carcinoid versus sclerosing hemangioma," respectively. The sensitivities for a diagnosis of neoplasia were 86.9% and 94.1% for nodules smaller than 1.1 cm in diameter and measuring 1.1 to 1.5 cm, respectively. The diagnostic accuracy of frozen sections was significantly better in nodules larger than 1.0 cm in diameter (p = 0.05). There were no false-positive diagnoses of malignancy, resulting in 100% specificity. CONCLUSIONS: Intraoperative consultation with frozen section is a sensitive and specific procedure for the diagnosis of malignancy from small pulmonary nodules. The distinction between BAC and atypical adenomatous hyperplasia, and of small peripheral carcinoid tumors from other lesions, can be difficult by frozen section. Thoracic surgeons need to become aware of these problems and develop appropriate therapeutic strategies.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

Evidence-based medicine, medical decision analysis, and pathology.

Recent advances in molecular pathology and other technologies such as proteomics present pathologists with the challenge of integrating the new information generated with high-throughput methods with current diagnostic models based mostly on histopathology and clinicopathologic correlations. Parallel developments in the field of medical informatics and bioinformatics provide the technical and mathematical methods to approach these problems in a rational manner. However, it remains unclear whether pathologists or other medical specialists will become primarily responsible for the development and maintenance of these multivariate and multidisciplinary diagnostic and prognostic models that are hoped to provide more accurate, individualized patient-based information. Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively new disciplines that use quantitative methods to assess the value of information, differentiate fact from myth, and integrate so-called best evidence into multivariate models for the assessment of prognosis, response to therapy, selection of laboratory tests, and other complex problems that influence individual patient care. We review from an epistemological viewpoint the current approach to information in pathology and describe some of the concepts developed by the practitioners of EBM and MDA.

Computational Biology↗
PubMed2004

Classification of individual lung cancer cell lines based on DNA methylation markers: use of linear discriminant analysis and artificial neural networks.

The classification of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) can pose diagnostic problems due to inter-observer variability and other limitations of histopathology. There is an interest in developing classificatory models of lung neoplasms based on the analysis of multivariate molecular data with statistical methods and/or neural networks. DNA methylation levels at 20 loci were measured in 41 SCLC and 46 NSCLC cell lines with the quantitative real-time PCR method MethyLight. The data were analyzed with artificial neural networks (ANN) and linear discriminant analysis (LDA) to classify the cell lines into SCLC or into NSCLC. Models used either data from all 20 loci, or from five significant DNA methylation loci that were selected by a step-wise back-propagation procedure (PTGS2, CALCA, MTHFR, ESR1, and CDKN2A). The data were sorted randomly by cell line into 10 different data sets, each with training and testing subsets composed of 71 and 16 of the cases, respectively. Ten ANN models were trained using the 10 data sets: five using 20 variables, and five using the five variables selected by step-wise back-propagation. The ANN models with 20 input variables correctly classified 100% of the cell lines, while the models with only five variables correctly classified 87 to 100% of cases. For comparison, 10 different LDA models were trained and tested using the same data sets with either the original data or with logarithmically transformed data. Again, half of the models used all 20 variables while the others used only the five significant variables. LDA models provided correct classifications in 62.5% to 87.5% of cases. The classifications provided by all of the different models were compared with kappa statistics, yielding kappa values ranging from 0.25 to 1.0. We conclude that ANN models based on DNA methylation profiles can objectively classify SCLC and NSCLC cells lines with substantial to perfect concordance, while LDA models based on DNA methylation profiles provide poor to substantial concordance. Our work supports the promise of ANN analysis of DNA methylation data as a powerful approach for the development of automated methods for lung cancer classification.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Telecytology of fine-needle aspiration biopsies of the pancreas: a study of well-differentiated adenocarcinoma and chronic pancreatitis with atypical epithelial repair changes.

Four experienced cytopathologists provided consultations using telecytology and routine microscopy. Twenty-seven fine-needle aspiration biopsies (FNABs) from patients with chronic pancreatitis with atypical epithelial repair changes (n = 9) and pancreatic low-grade adenocarcinomas (LG-AC) (n = 18) were studied. False-positive and false-negative diagnostic rates were 19.4% and 12.5% by microscopy and 11.1% and 2.8% by telecytology. Comparisons of agreements between the correct diagnoses and consultations rendered by the two methods and among the diagnoses rendered on the same cases by the two modalities yielded kappa coefficients ranging from 0.444-1.000. Telecytology yielded slightly better kappa coefficients than microscopy. This method, which to our knowledge has not been previously applied to pancreatic FNAB, provides a potentially useful consultative tool for the interpretation of these difficult specimens. The diagnosis of FNAB from patients with chronic pancreatitis and LG-AC is difficult even for experienced consultants, as underscored by the considerable intraobserver and interobserver variability encountered in this study.

Biopsy, Needle↗
PubMed2003

The prognostic significance of intranodal isolated tumor cells and micrometastases in patients with non-small cell carcinoma of the lung.

OBJECTIVE: To study whether isolated tumor cells and micrometastases, as defined by the current American Joint Committee on Cancer criteria for extrapulmonary neoplasms, have prognostic value for patients with resected non-small cell carcinoma of the lung. METHODS: Intrathoracic lymph nodes (n = 1063) from 60 patients with non-small cell carcinoma of the lung were studied for the presence of metastases with serial histologic sections and keratin immunostains. Metastases were classified as isolated tumor cells, pN1mi, pN1, pN2mi, and pN2. Isolated tumor cells were smaller than 0.2 mm, while pN1mi and pN2mi measured 0.2 mm to 2 mm. Survival analysis was performed, stratifying by nodal status and stage. RESULTS: Isolated tumor cells were detected in 11 lymph nodes from 5 of 33 pN0 patients and in 9 pN1 and pN2 patients. The lymph nodes from 3 patients were reclassified as pN1mi. No pN2mi were detected. A survival model based on a stratification of the cohort into stages I to III was significant (chi-square = 7.426, df = 2, P =.024) but demonstrated considerable overlap between the survival curves of stage I and II patients. A model stratifying isolated tumor cells and pN1mi into stage I disease was significant (chi-square = 7.985, df = 2, P =.018) and showed no overlap between the survival curves of stage I and II patients. There were no significant survival function differences between patients with pN0, isolated tumor cells, and pN1mi. CONCLUSIONS: Patients with non-small cell carcinoma of the lung with isolated tumor cells and pN1mi have similar survivals to those with pN0, consistent with the findings reported for breast cancer patients. Future larger studies of patients with non-small cell carcinoma of the lung are needed to confirm whether current American Joint Committee on Cancer staging criteria should be modified to include the pN1mi category.

Adenocarcinoma↗
PubMed2003

Self-instructional "virtual pathology" laboratories using web-based technology enhance medical school teaching of pathology.

Second-year medical students have traditionally been taught pulmonary pathophysiology at the University of California-Los Angeles (UCLA) School of Medicine using lectures, discussion groups, and laboratory sessions. Since 1998, the laboratory sessions have been replaced by 4 interactive, self-instructional sessions using web-based technology and case-based instruction. This article addresses nature of transformation that occurred from within the course in response to the infusion of new technologies. The vast majority of the course content has been digitized and incorporated into the website of the Pathophysiology of Disease course. The teaching histological slides have been photographed digitally and organized into "cases" with clinical information, digital images and text, and audio descriptions. The students study the materials from these cases at their own pace in 2 "virtual pathology" laboratory, with a few instructors supervising the on-site sessions. The students discuss additional cases available on the website in 2 other laboratory sessions supervised by a pulmonologist and a pathologist. Marked improvement in student participation and satisfaction was seen with the use of web-based instruction. Attendance at laboratory sessions, where the students had previously been required to bring their own microscopes to study histological slides at their own pace, increased from approximately 30% to 40% of the class in previous years to almost 100%. Satisfaction surveys showed progressive improvement over the past 4 years, as various suggestions were implemented. The value of web-based instruction of pathology at the UCLA School of Medicine is discussed.

California↗
PubMed2003

Current controversies regarding the role of asbestos exposure in the causation of malignant mesothelioma: the need for an evidence-based approach to develop medicolegal guidelines.

Asbestos is a group of fibrous silicate minerals that includes two mineralogic groups: amphiboles and serpentines. While the carcinogenic role of amphiboles (eg, crocidolite and amosite) is well established, medical "experts" that tend to strongly advocate their views currently argue in medicolegal cases multiple specific issues regarding the carcinogenicity of asbestos fibers. For example, it is controversial whether chrysotile causes malignant mesothelioma (MM); what are the specific carcinogenic thresholds for amphiboles and chrysotile; what occupations are truly at risk to develop MM as a result of asbestos exposure; what is the role of chrysotile in the development of peritoneal MM; how to assign causation in individuals exposed to multiple industrial products containing variable concentrations of various asbestos fibers; and, what criteria should be used to accept causation in household exposure cases and others. The causation criteria currently acceptable in U.S. courts are surprisingly flexible and subject to variable interpretation by medical "experts." At a time where thousands of individuals are claiming causation of MM by asbestos exposure, there is a need to develop more specific causation guidelines based on scientific evidence. Evidence-based medicine has been proposed as a new approach to the study, teaching, and the practice of medicine and has been used as a process of systematically reviewing the relevant studies in the literature to assess their scientific validity and development of guidelines. This article summarizes some of the current controversies regarding the role of asbestos exposure in the causation of MM and suggests the need for future evidence-based medicine-type studies to develop causation guidelines that could be used consistently during litigation.

Animals↗
PubMed2003

Malignant monotypic epithelioid angiomyolipoma of the retroperitoneum.

Monotypic epithelioid angiomyolipoma (EAML) is an uncommon variant of angiomyolipoma, occurring primarily in the kidney and characterized by a predominance of HMB-45-positive epithelioid cells. EAML is generally considered a benign neoplasm, though rare cases exhibiting malignant behavior have been reported. We describe a patient with a primary retroperitoneal monotypic EAML, composed exclusively of atypical epithelioid cells, which metastasized to the liver and the mediastinum. This case represents, to our knowledge, the first description of metastatic disease occurring in an EAML of this particular site.

Adult↗
PubMed2003

Virtual microscopy as a tool for proficiency testing in cytopathology: a model using multiple digital images of Papanicolaou tests.

BACKGROUND: Modern digital cameras can acquire images from cytologic slides at sufficient resolution to allow for digital enlargement and scrolling on a video monitor, allowing for the simulation of microscopy using a computer. OBJECTIVE: The purpose of this study was to develop a tool for proficiency testing in cytopathology using multiple digital images of Papanicolaou tests. METHODS: Nine images were photographed from each of 10 Papanicolaou tests at x100 optical magnification, 3400 x 2300-pixel resolution, using a light microscope and a digital camera. All images from each case were tiled in a single canvas with Photoshop 4.0 software. Two cytopathologists and 3 cytotechnologists interpreted these "virtual slides" using a computer and graded diagnostic codes (PAP program, College of American Pathologists). Subjects were retested a year later using the glass slides from the same cases and routine microscopy. Both test results, by diagnostic code, were compared with the McNemar test of symmetry. RESULTS: The 5 test subjects provided 42 and 50 correct diagnostic codes by "virtual microscopy" and light microscopy, respectively. No significant asymmetry in results obtained by virtual microscopy and light microscopy was encountered with the McNemar test of symmetry. All test answers were correctly classified by selection series, using both virtual microscopy and light microscopy, and the responses would have been graded as 100% by current PAP program scoring guidelines. This suggests that virtual microscopy could be used for proficiency testing purposes. CONCLUSIONS: A simple virtual microscopy method designed to challenge participants to locate and diagnose cells of interest was effective for the administration of standardized proficiency tests. Virtual microscopy methods that rely on single-plane images to locate and diagnose cells of interest could provide effective proficiency testing tools prior to the development of more computationally intensive systems that represent an entire Papanicolaou test at multiple focal planes.

Computer Simulation↗