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Nuclear chromatin texture in rectal cancer. Relationship to tumor stage.
Rosito MA, Moreira LF, da Silva VD, Damin DC, Prolla JC.
Department of Coloproctological Surgery and Laboratory of Cytopathology, Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
OBJECTIVE: To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas classified according to Dukes staging. STUDY DESIGN: High-resolution imagery of 6,001 nuclei from 51 specimens of rectal carcinoma and 22 specimens of normal rectal tissue was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to form a characteristic signature. RESULTS: Rectal carcinomas were significantly different from normal rectum in their digital signature. Eleven karyometric features, such as nuclear area and total optical density, were clearly different between the groups, with significant differences found in analysis of 8 of those features. The most distinctive pattern in lesion signatures in comparison with normal rectal tissue was observed at Dukes' stage D. However, the highest average signature values were seen at Dukes' stage B. The lesion signatures and total optical density observed in cancer specimens deviated markedly from values in the normal group. CONCLUSION: Chromatin texture signature proved to be a useful method of identifying and characterizing nuclear differences between rectal carcinoma and normal rectal tissue.
PMID: 12630079 [PubMed - in process]
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Karyometry in Barrett's esophagus.
da Silva VD, Prolla JC, Sharma P, Sampliner R, Thompson D, Bartels PH.
Department of Pathology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
OBJECTIVE: To derive a progression curve for lesions in Barrett's esophagus based on karyometric features. STUDY DESIGN: High-resolution imagery of 900 nuclei from normal gastric tissue, Barrett's metaplasia, Barrett's high grade dysplasia and adenocarcinoma of the esophagus was recorded. Karyometric features were computed, and nuclear signatures and lesion signatures for these lesions were derived. A progression curve was defined. RESULTS: Esophageal lesions were distinctly different from the normal gastric fundus tissue, with nuclei from Barrett's metaplasia deviating from normal almost as much as nuclei from high grade dysplasia and adenocarcinoma. There was considerable case-to-case variability and overlap between lesions histologically assigned to different diagnostic categories. CONCLUSION: The karyometric data suggest that Barrett's metaplasia is a more developed lesion than previously assumed.
PMID: 11233742 [PubMed - indexed for MEDLINE]
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Imagequest. A model self-assessment and self-teaching program for cytopathology.
Prolla JC, da Silva VD, Muller RL, Muller RL.
Hospital de Clinicas de Porto Alegre, Cytopathology Laboratory, Brazil.
OBJECTIVE: To develop a low-cost program for providing self-assessment and training for cytopathologists. STUDY DESIGN: Using an optical microscope with a color charge coupled device connected to a personal computer equipped with an ISA bus frame grabber, images were digitized. After the selection of proper images, they were attached to 100 questions with a single answer and five options each. For every question, references accompanied the answer. A colorful score and sounds were played while each question and its corresponding answer were on the screen in order to stimulate the learning process. RESULTS: A low-cost, attractive, effective program for providing self-assessment and training for cytopathologists was developed. CONCLUSION: The use of a high-level programming language permits the creation of a simple, assisted, programmable interface with accessibility for upgrades and customization for every pathologist. This feature permits the insertion of new questions, an essential feature to preserve the usefulness of the program for the future.
PMID: 9305390 [PubMed - indexed for MEDLINE]
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Comparison of conventional microscopy and digitized imaging for diagnosis in serous effusions.
da Silva VD, Prolla JC, Diehl AR, Baldo MF, Muller RL.
Hospital de Clinicas de Porto Alegre, Brazil.
OBJECTIVE: To compare diagnoses made from conventional microscopy and digitized imaging in preparation for teleconsultation cytopathology services that are affordable and efficient. STUDY DESIGN: One hundred six consecutive serous effusions received in the cytopathology laboratory of a general hospital in Porto Alegre, RS, Brazil, were studied. The diagnoses by the senior cytopathologist at the conventional microscope were considered the standard and identified 61 cases negative and 45 positive for malignant cells (40 epithelial and 5 nonepithelial). The same pathologist digitized 461 selected fields for analysis by a second experienced cytopathologist (observer A) and a senior cytotechnologist (observer B) without knowledge of the standard diagnoses. Ten cases were studied in daily sessions of one hour each. The diagnoses were negative for malignant cells, positive for malignant cells (epithelial) and positive for malignant cells (nonepithelial). RESULTS: The following kappa values were found: 0.91 (observer A and observer B versus standard) and 0.86 (observer A versus observer B). CONCLUSION: Remote digitized imaging diagnosis in serous effusions is possible and has a high degree of concordance with diagnosis by conventional microscopy. Similar studies involving a larger group of cytopathologists and cytotechnologists should be done to identify interobserver variability.
PMID: 9196802 [PubMed - indexed for MEDLINE]
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Digital karyometry in pancreatic adenocarcinoma.
Bersch VP, da Silva VD, Osvaldt AB, da Costa MS, Rohde L, Mossmann D.
Federal University of Rio Grande do Sul Medical School, RS, Brazil. [email protected]
OBJECTIVE: To characterize nuclei from pancreatic adenocarcinoma and nonneoplastic pancreatic tissue by digital karyometry, demonstrating specific nuclear signatures for each of them. STUDY DESIGN: Of cells from malignant and nonmalignant pancreatic tissue, 1,300 nuclei were assessed by digital karyometry from paraffin blocks stored at the Pathology Service of Hospital de Clinicas de Porto Alegre. A set of 40 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus. Signatures were created for both types of tissue, and a distance metric from "normal" was defined and calculated for them. RESULTS: There were significant differences in 11 features between the 2 groups, allowing the creation of digital signatures. CONCLUSION: Nuclear chromatin texture signature can offer a specific digital characterization for both pancreatic adenocarcinoma and nonmalignant pancreatic tissue. Several isolated nuclear features serve as markers for the diagnosis of pancreatic adenocarcinoma. The present karyometric study of normal and malignant pancreatic tissue may be of use as a continuing tool to early diagnosis of pancreatic adenocarcinoma as it can be applied to cytologic specimens, also. In the future, studies using this technique should assess the chemopreventive potential of different agents as well as prognosis and treatment options for pancreatic adenocarcinoma.
PMID: 12746980 [PubMed - in process]
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Angiogenesis in advanced colorectal adenocarcinoma with special reference to tumoral invasion.
Tarta C, Teixeira CR, Tanaka S, Haruma K, Chiele-Neto C, da Silva VD.
Department of Surgery and Pathology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. [email protected]
BACKGROUND: Angiogenesis is a crucial step in tumor growth and progression. Its quantification by microvessel counting has a prognostic value in several types of malignancies and recently has been appraised in gastrointestinal tumors. AIM: To assess the prognostic significance of microvessel quantification in colorectal carcinomas, studying its association with hematogenous metastases, survival and clinicopathological variables such as size, histologic differentiation and depth of tumoral invasion. PATIENTS/METHODS: Forty eight patients with colorectal adenocarcinoma were included in this study. Histologic sections of invasion tumoral margin (4 microns) were analyzed and endothelined microvessels were immunostained with monoclonal mouse Von Willebrand Factor (anti-FVIII). The microvessel count was performed from the identification of the area with increased microvessel density--hot spots--and results of the mean in five of these fields. RESULTS: The cut-off microvessel count was 14 microvessels/0.785 mm2, which divided the sample into hypovascular and hypervascular groups. While 2/8 (25%) tumors with muscularis propria invasion were classified as hypervascular, 11/15 (73%) tumors with serosa or perivisceral fat were classified as hypervascular. However, a non-significant statistical association was found between the angiogenesis quantification, hematogenous metastases, survival and clinicopathological variables such as size and histologic differentiation of the tumor. CONCLUSIONS: The findings of significantly increase of microvessel count in conformity with tumoral invasion depth supports the hypothesis that tumor progression might be related to angiogenesis. Although angiogenesis is an important step in the tumoral growth and during the metastatization process, other factors can be implicated.
Publication Types:
PMID: 12184164 [PubMed - indexed for MEDLINE]
Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.
Montironi R, Thompson D, Scarpelli M, Bartels HG, Hamilton PW, da Silva VD, Sakr WA, Weyn B, van Daele A, Bartels PH.
Institute of Pathological Anatomy and Histopathology, University of Ancona, 60020 Torrette, Italy. [email protected]
OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.
Publication Types:
PMID: 12037030 [PubMed - indexed for MEDLINE]
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Quantitative study of ductal breast cancer progression: nuclear signatures for evaluation of progression grade.
Mombello A, Mariuzzi L, Morelli L, Granchelli G, Rucco V, Tarocco E, da Silva VD, Thompson D, Bartels HG, Bartels PH, Mariuzzi G.
Dipartimento di Patologia, Sezione di Anatomia Patologica, Policlinico GB Rossi, Strade Le Grazie, 8. 37134 Verona, Italy. [email protected]
The evaluation of progressive morphological changes, with 93 morphometric parameters in tissue lesions representative of ductal breast cancer progression, has been performed in order to define in great detail the profile of chromatin texture (nuclear signature) changes. A gradual, distinctive increase in nuclear signature alterations from hyperplasia to infiltrating carcinoma has been found. The nuclear signatures' analysis of microinfiltrating foci in comedo DCIS showed sharp differences compared with those of comedo DCIS they derived from: these foci consist of cells with smaller and also more homogeneous nuclei. Opposite to the prominent heterogeneity of those of comedo DCIS: they appear to express a reduced clonality in the new, more progressed, cell population. Digital analysis of chromatin patterns seems to be useful, beyond mere extraction of individual features of value, in getting objective data for individual grading and prognosis of breast cancer.
PMID: 11753877 [PubMed - indexed for MEDLINE]
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Measurement of chemopreventive efficacy in skin biopsies.
Bozzo P, Alberts DS, Vaught L, da Silva VD, Thompson D, Warnecke J, Miller RC, Einspahr J, Bartels PH.
Department of Surgery, Arizona Cancer Center, University of Arizona, Tucson 85724-05024, USA.
OBJECTIVE: To explore methods suitable for quantitative assessment of the efficacy of chemopreventive intervention. STUDY DESIGN: High-resolution imagery of nuclei from the suprabasal and basal cell layers of sun-damaged skin were recorded. There were 10 cases. A shave biopsy was taken from an area of clearly evident solar keratosis before and after treatment with 2-difluoromethyl-dlornithine (DFMO) and from the colateral forearm, treated with a placebo. A number of karyometric variables were computed and combined to derive marker features that provided a numeric measure of the degree of nuclear deviation from normal. RESULTS: DFMO treatment was effective overall in reducing the degree of nuclear abnormality seen in the biopsies; in 8 of the 10 cases there was a significant improvement. The placebo-treated arm did not show a statistically different abnormality from the untreated arm. CONCLUSION: Karyometric analysis can provide numeric measures that allow documentation of statistically significant regression of actinic keratotic lesions following treatment with DFMO.
Publication Types:
PMID: 11531145 [PubMed - indexed for MEDLINE]
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Progression curves for endometrial lesions.
Bartels PH, Garcia FA, Davis J, da Silva VD, Bartels HG, Thompson D, Alberts DS.
Arizona Cancer Center and Optical Sciences Center, University of Arizona, Tucson, Arizona, 85721 USA.
OBJECTIVE: To derive a numeric measure for the progression of endometrial lesions as a baseline study for an eventual assessment of chemopreventive intervention efficacy. STUDY DESIGN: Tissue sections from normal endometrium at the proliferative and secretory phase, simple hyperplasia, atypical hyperplasia from cases free of concomitant adenocarcinoma and adenocarcinoma of the endometrium were recorded at high spatial resolution. Six cases from each diagnostic category were chosen as "typical," and 60 epithelial nuclei were randomly selected for measurement for each case. Discriminant analyses were carried out to derive a direction of progressive change in feature space and to correct the progression curve for the presence of cells not expressing progressive change among the random sample of nuclei. RESULTS: A well-conditioned progression curve was derived based on the mean discriminant function scores for each diagnostic category and the mean nuclear abnormality of the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. The lesion signatures showed a clear trend toward extension into the range of higher nuclear abnormalities with increasing progression. There was an indication that abnormal endometrial lesions may comprise cases with distinctly different degrees of nuclear abnormality. CONCLUSION: A numeric assessment of lesion progression for endometrial lesions, based on karyometric measurements, is possible. The data suggest that additional analysis may provide further characterizing information for individual lesions.
PMID: 11233737 [PubMed - indexed for MEDLINE]
Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.
Weyn B, Jacob W, da Silva VD, Montironi R, Hamilton PW, Thompson D, Bartels HG, Van Daele A, Dillon K, Bartels PH.
Center of Electron Microscopy, University of Antwerp, Antwerp, Belgium. [email protected]
BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions. Copyright 2000 Wiley-Liss, Inc.
PMID: 11002269 [PubMed - indexed for MEDLINE]
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Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.
da Silva VD, Montironi R, Thompson D, Bartels HG, Vaught L, Hamilton PW, Bartels PH.
Federal University of Rio Grande do Sul, Porto Alerge, Brazil, Institute of Pathological Anatomy and Histopathology, University of Ancona, Italy.
OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.
PMID: 10560478 [PubMed - indexed for MEDLINE]
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A remote second-look teleconsultation protocol on breast cytopathology.
da Silva VD.
University of Arizona Optical Sciences Center, Tucson, USA.
PMID: 10221009 [PubMed - indexed for MEDLINE]
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Chromatin texture signatures in nuclei from prostate lesions.
Bartels PH, da Silva VD, Montironi R, Hamilton PW, Thompson D, Vaught L, Bartels HG.
Optical Sciences Center, University of Arizona, Tucson 85721, USA.
OBJECTIVE: To characterize nuclei from prostatic lesions in a highly specific manner by developing a nuclear chromatin texture signature and to characterize lesions by means of their composition of nuclei with diverse degrees of deviation from normal. STUDY DESIGN: High-resolution digitized imagery of nuclei from normal prostates, from prostatic neoplastic lesions of low and high grade and from histologically normal appearing regions of prostates with low and high grade prostatic intraepithelial neoplasia (PIN) lesions were recorded. A set of 65 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus. These features were arranged and processed to form a distinctive signature. A distance metric from "normal" was defined and computed for each nucleus. RESULTS: Profiles of feature values can, after suitable scaling, be presented as distinctive feature value signatures. For many practical applications, profiles based on a standardized distance from normal nuclei may be more useful. Such profiles allow the derivation of a progression curve, showing increasing distances for diagnostic groups with increasing lesion progression up to high grade PIN lesions. Within each diagnostic group different cases show distinctive distributions of nuclei with differing degrees of deviation from normal, allowing the derivation of a lesion signature. CONCLUSION: Nuclear chromatin texture signatures may be of value for the characterization of both nuclei and lesions. They are based on a more comprehensive use of information offered by the nuclear chromatin pattern than that included in classification methods. While these signatures offer a more specific characterization of a clinical sample, they also are subject to more variability within a diagnostic category. This may not be due to randomness but may reflect some actual differences between lesions.
PMID: 9801759 [PubMed - indexed for MEDLINE]
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