Correspondence Re: T.J. Flotte. Research by pathologists in the United States: analysis of publications. Mod Pathol 6:484, 1993.
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Biomedical subjects
Publications and source records attributed to J J Berman.
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Pathology departments devote considerable energy toward indexing diagnoses. To date, there have been no detailed tabulations of the results of these efforts. We have thoroughly analyzed three years' surgical pathology reports (40,124) generated for 29,127 different patients from the University of Florida at Gainesville between Jan 1, 1990, and December 31, 1992. 64,921 SNOMED code entries (averaging 1.6 codes per specimen and 1.4 specimens per patient) were accounted for by 1,998 distinct SNOMED morphologies. A mere 21 entities accounted for 50% of the morphology code occurrences. 265 entities accounted for 90% of the morphology code occurrences, indicating that the diagnostic efforts of pathology departments are contained within a small fraction of the many thousands of morphologic entities available in the SNOMED nomenclature. One of the key problems in using SNOMED data collected from surgical pathology reports is the redundancy of lesions reported for single patients (i.e., a patient's disease may be coded on more than one specimen from the patient, leading to false conclusions regarding the incidence of disease in the population). In this study, redundant SNOMED data was removed by eliminating repeat morphology/topography pairs whenever they occur for a single patient. SNOMED data can be stratified on the basis of age and sex (data fields included on every surgical pathology report). This analysis represents the first published analysis of SNOMED data from a large pathology service, and demonstrates how SNOMED data can be compiled in a form that preserves patient privacy.
Medical coding has become an important new industry that has originated from the field of medical informatics. Automatic coding of specimens has emerged as a way of relieving hospitals from the cost of paying professional coders and for achieving uniform coding for all specimens. Unfortunately, automatic coding, like manual coding, has numerous pitfalls. Further, the coding algorithms employed by manufacturers of automatic coders are typically proprietary. We have developed a method for automatic coding of pathology reports. Using this public domain autocoder, we have previously demonstrated that automatic SNOMED coding was superior to manual coding in several measurable categories, including the overall number of codes generated and the number of distinct code entities provided. In this report, we describe an algorithm that executes this strategy in the M-Technology environment.
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Premalignant lesions occur early in neoplastic development, are often small and multiple, lack one or more of the properties of cancers, often regress, and are often easily treatable. Such lesions may be derived from epithelial or nonepithelial cell populations. Many epithelial premalignant lesions can be identified by their confinement by a basement membrane. Mesenchymal, hematologic, and lymphoid premalignant lesions are difficult to recognize as most of these lesions have no defining morphologic features or anatomic boundary that identifies their premalignant nature. We have devised a classification for nonepithelial premalignant lesions, based on biologic behavior rather than morphology, that includes neoplastic lesions that have some but not all of the properties generally attributed to developed cancers. The five categories of nonepithelial premalignant lesions are: (a) lesions delimited by a basement membrane (e.g., melanoma in situ); (b) nonepithelial neoplasms having a low rate of metastasis (e.g., giant cell tumor of bone); (c) early forms of nonepithelial malignancy (e.g., Kaposi's sarcoma, patch stage); (d) indolent neoplasms that regularly progress to malignancies (e.g., chronic lymphocytic leukemia); and (e) certain low-grade neoplasms derived from germ cells (e.g., Grade 1 immature teratoma). Formal classification of the nonepithelial premalignant lesions would allow the pathologist to diagnose these biologically distinct entities as something other than simply benign or malignant, and would direct tumor biologists to study the key molecular properties that control the premalignant phenotype.
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The National Cancer Institute established the Registry of Experimental Cancers in March 1970. This registry consists of a permanent collection of pathological materials on spontaneous and induced lesions in laboratory animals that includes histological slides, paraffin blocks, autopsy findings, pathological diagnoses, photographs, and experimental records. The material presently is composed of approximately 60,000 consecutive records and is a valuable resource for researchers interested in tumors and other lesions arising spontaneously or from specific induction protocols in experimental animals. The entire registry database was transferred to an object-oriented database that permits registry staff to write programs for the different data field objects, thus customizing searches and other database functions. Twenty-seven animal species are represented and a total of 6,496 diagnostic entities and 1,106 treatment and control protocols are listed. Archival material may be retrieved for analysis of molecular markers.
Liver cell dysplasia is characterized by hepatocellular foci with nuclear atypia. It is often seen in cirrhosis and may be a precursor of hepatocellular carcinoma (HCC). To determine whether liver cell dysplasia is DNA aneuploid, 72 sections of 33 cirrhotic livers from the autopsy files of The Johns Hopkins Hospital were studied, and 14 foci of dysplasia from 13 cirrhotic livers were selected. Patients ranged in age from 32 to 70 years. Histologically, there were 10 foci of low-grade dysplasia and four foci of high-grade dysplasia. Nine HCCs served as positive controls; seven autopsy livers with no morphologic or clinical evidence of primary liver disease served as negative controls. One focus of HCC and one focus of dysplasia were unsatisfactory for analysis. Flow cytometric examination demonstrated subpopulations with DNA abnormality in four of nine (44%) foci of low-grade dysplasia, of which three were aneuploid. Three of four (75%) foci of high-grade dysplasia were aneuploid. Six of eight (75%) HCCs showed DNA abnormality, of which five were aneuploid. DNA aneuploidy was not present in the seven control livers; however, one showed DNA abnormality. We conclude that liver cell dysplasia is a morphologic entity that contains DNA aneuploid cells, a feature that supports the role of liver cell dysplasia in the evolution of HCC.
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Regional blood centers recently increased the number of tests used to protect transfusion recipients from infectious disease. The Food and Drug Administration has noted that computer systems for managing these data have lost donor data or failed to recognize all deferrals. Of 118,396 consecutive donations, including 4,859 records with at least one positive test result, records were analyzed to determine the number and frequency of distinct combinations of test data. A modular precedence-logic expert system assigned donor deferrals and unit dispositions. Ten combinations of data accounted for 4,334 records (89%); the remaining 525 records (11%) were distributed among 85 combinations of test data. The expert system correctly assigned all records. Regional blood centers must interpret a growing number of test results, including donations with a complicated pattern of multiple positive screening test results. The distribution of these data is described and the expert system's ability to monitor deferrals and ensure database completeness is demonstrated.
A variety of experimental and clinical examples of preneoplasia demonstrate that regression of early lesions is common. This paper examines the hypothesis that early lesions operate under the identical growth kinetics of 'late' lesions (neoplasms), but that kinetic features favouring continuous growth in established lesions tend to favour extinction of lesions composed of small numbers of cells. Growth simulations of early lesions were produced using the Monte Carlo method, a technique demanding intensive computations. With the advent of powerful personal computers, this technique is now widely available to biologists. Simulating growth under conditions of cell loss similar to those observed in established tumours, the model predicts that the great majority of initiated cell clusters are expected to reach extinction within a few cell doubling times, and most early (promoted) lesions would not likely progress to the size of a clinically detectable lesion within the life span of the host organism. These Monte Carlo simulations provide a model of initiated cell growth consistent with the recently demonstrated role of early lesion cell death in the development of human lymphomas and in transgenic mice expressing the bcl-2 oncogene. The model demonstrates that small increments in the intrinsic cell loss probability in even the earliest progenitors of malignancy can strongly influence the subsequent development of neoplasia from initiated foci.
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The paradigm of pathology research as an endeavor among grant-funded principal investigators resulting in first-author publications is unsupported by quantitative examination of author profiles extracted from the scientific literature. Publications in six pathology journals (Modern Pathology, American Journal of Surgical Pathology, Human Pathology, Acta Cytologica, Archives of Pathology and Laboratory Medicine, and American Journal of Clinical Pathology) and three general science journals (Science, New England Journal of Medicine, and Proceedings of the U.S. National Academy of Sciences) were reviewed. Twenty articles per journal from each of three years (1987, 1989, and 1991) were examined (a total of 520 articles). Of these, 295 articles were first-authored by a member of a department of pathology. Of the 295 articles first-authored by a member of a pathology department, 47 (16%) articles listed competitive grant support. Of the grant-supported articles, 20 articles listed NIH support, but only four had an NIH-supported principle investigator as the first author of the article. Unfunded research represented the vast majority (84%) of work produced by pathologists. A review of the ISI Citation Index showed that those articles written by funded pathologists averaged 8.7 (S.D. 7.8) citations per article, compared to 10.4 (S.D. 12.1) citations per article for unfunded pathologists. Results suggest that unfunded research accounts for the majority of pathology research activity as well as their resulting literature citations.
Current cancer treatment protocols are designed to release the tumour burden down to a small number of cells. In this study, we use Monte Carlo simulations to show that small populations of cells with intrinsic cell loss rates comparable to the cell loss rates observed clinically in human tumours, may regress spontaneously. Large populations of cells tend to grow under the same conditions of cell loss that result in extinction of small clones. Furthermore, minor variations in the intrinsic cell death probability near 0.50 result in large differences in the number of surviving cells calculated at the 100th generation. When Monte Carlo simulations of clonal growth resulted in clones with large populations (> 50 cells), the population as a whole behaved in a deterministic fashion (logarithmic growth) similar to those observed in clinically observed neoplasms and consistent with other published models of tumour growth. These findings provide a plausible explanation for the clinically observed failure of tumours to recur in instances where tumour burden remains following cancer therapy. The findings also demonstrate the usefulness of the Monte Carlo method to simulate biologic events in populations where the fate of each member of a population can be modeled probabilistically.
Keratoacanthomas (KAs) are rapidly growing cutaneous lesions that frequently look much like well-differentiated squamous cell carcinomas (SCCs) but spontaneously regress. It is uncertain whether KA is a reactive hyperplastic lesion that mimics a neoplasm or a true (but defective) neoplasm that cannot sustain progressive growth. To address this question, we performed DNA flow cytometric analysis on 14 KAs and 10 cutaneous SCCs for comparison. By multiparameter DNA flow cytometry using forward scatter and orthogonal scatter, 10 KAs and 4 SCCs had peridiploid DNA aneuploid populations (DNA indices of 1.03-1.14), and 2 SCCs had grossly aneuploid populations (DNA index, 1.69 and 2.33). Our data thus support aneuploidy in KAs. It is argued that KA is a true neoplasm.
Basaloid squamous carcinoma is believed to be a histologically distinct variant of squamous cell carcinoma of the neck region with 11 cases reported. Two cases arising in the pyriform fossa and vallecula are reported, both of which were associated with second primary malignant tumors: esophageal small cell carcinoma and palatal squamous cell carcinoma, respectively. The authors suggest that basaloid squamous carcinoma may be associated with a high incidence of second primary tumors in the upper gastrointestinal tract or larynx.