Biomedical subjects

J C Fleege

Publications and source records attributed to J C Fleege.

8 recordsLinked to original sources

PubMed1992

Quality control methods for data entry in pathology using a computerized data management system based on an extended data dictionary.

In pathology, computerized data management systems have been used increasingly to facilitate a more efficient supply of information. Since data entry precedes data utilization, the reliability of the information stored strongly depends on the quality of data input. Despite its potential capability, most personal computer-based database software does not provide versatile and user-friendly data validation procedures. Therefore, we developed a data dictionary-driven data management system that enables the user to perform extensive validation routines without the need for hard programming. Using examples from an existing database for endometrial carcinomas, different types of data errors and their error traps are explained. It is pointed out that data type definitions, defaults, templates, or picture clauses are suitable means to avoid formal errors. Validations on data domains and ranges test whether data fall into a predefined scope. Relational checks control data validity within a context of different data items, whereas process routines provide automatic data computation, thereby circumventing user input. By exploiting the facilities of an extended data dictionary, a powerful tool is made available to secure various aspects of data integrity simultaneously with input. In this way, computerized data quality control can improve the efficiency and reliability of data management tasks in pathology.

Medical Informatics Computing↗

PubMed1992

Syntactic structure analysis in invasive breast cancer: analysis of reproducibility, biologic background, and prognostic value.

The reproducibility, biologic background, and prognostic value of syntactic structure analysis were studied in a group of 94 patients with invasive primary breast cancer. Using an interactive digitizing video overlay system, the centers of malignant breast cancer nuclei were marked in the five (subjectively) most cellular fields of vision for each case at a final magnification of X1,200, and the corresponding minimum spanning tree was composed for each field. From each minimum spanning tree, 10 syntactic structure features were derived; subsequently, the mean, standard deviation, minimum, and maximum values of the five fields analyzed were calculated for further statistical analysis. Forty statistics thus were available for each case. The reproducibility of repeatedly measuring the same field (independent of nuclearity) and the same patient twice by the same or different observers was good for most of the syntactic structure features. When comparing the statistics of the syntactic structure features with other established prognosticators, correlations were found with (in this order) standard deviation and mean nuclear area (expressing nuclear differentiation), volume percentage epithelium (expressing architectural differentiation), and mitotic activity index. In univariate survival analysis several syntactic structure statistics yielded prognostic significance, the best being the maximum of the number of nuclei with two neighbors (P = .002; Mantel-Cox test, 12.4). Multivariate analysis revealed that syntactic structure features did not provide additional prognostic values with regard to each other. However, they did show additional prognostic values with regard to the multivariate prognostic index (currently one of the best prognosticators in breast cancer), which combines the mitotic activity index, lymph node status, and tumor size. Measurement of syntactic structure features could therefore contribute to an improved prediction of prognosis of breast cancer patients. In conclusion, syntactic structure analysis is a simple, fast, and highly reproducible technique that shows prognostic value in invasive breast cancer and also has important prognostic value with regard to the well-established and prognostically strong morphometric features. It seems to be a promising new method of analyzing tissue architecture in breast cancer and perhaps in many other tumors.

Breast Neoplasms↗

PubMed1992

Assessment of the risk on endometrial cancer in hyperplasia, by means of morphological and morphometrical features.

The value of two "cancer risk" assessment rules (one consisting of qualitative microscopical features and one consisting of morphometric characteristics) has been evaluated in 39 patients with hyperplasia of the endometrium. Of these, in seven (7139 = 18%) cancer was detected in the follow-up and 32 remained stable or became less abnormal. The results of the qualitative analysis were well in agreement with those published earlier. In none of the eight patients with simple hyperplasia cancer was detected, in contrast to five of the 11 patients (45%) with cytologic atypia and glandular complexity. Twenty patients showed cytologic atypicality in the absence of glandular complexity, or no atypicality but glandular complexity; in two (10%) of these patients cancer was detected later in the follow-up. The morphometric rule (consisting of volume percentage of stroma, log-normally transformed standard deviation of the shortest nuclear axis and outer surface density of the glands) results in a multivariate score. Nineteen patients had a score value above 0.6 and in none of them cancer was found. In contrast, in seven of the 20 patients (35%) with a score value below 0.6, cancer was detected. Regarding the question which of the techniques is more powerful, the specificity is better with the qualitative evaluations; the sensitivity is higher with the morphometric rule. An advantage of the morphometric rule is that only two groups (very low/very high risk) are discerned.

Endometrial Hyperplasia↗

PubMed1992

Intra-patient variation between breast cancer axillary lymph node metastases using quantifiable features.

The intra-patient variations of some clinically relevant quantifiable features, between axillary lymph node metastases were evaluated in 44 breast cancer patients. In all lymph node metastases detected (range 2-33 per patient), the mitotic figures were counted, the volume percentage epithelium was assessed and the mean nuclear area was measured. The intra-patient variation for each quantifiable feature was expressed by the coefficient of variation (CV). Since the measurement techniques used introduce a certain, well known variation themselves because of sampling and measurement errors, the CVs found had to be greater than methodological tolerance limits (established in previous studies) to be interpreted as indicating biological variation. The CVs exceeded the methodological tolerance limits in 86% of the cases for the mitotic count, in 48% of the cases for the volume percentage epithelium, and in 47% of the cases for the mean nuclear area. This indicated that in these cases, the variation found in the quantifiable features could not be explained by sampling or measurement errors and should be regarded as real biological variation. Furthermore, the variation in the quantifiable features studied showed a significant positive correlation with the number of lymph node metastases. Thus, there may be considerable intra-patient variation in quantifiable features between axillary lymph node metastases in breast cancer. This may indicate that these lymph node metastases originate independently from different clones within the primary tumour, that they are independently formed in different stages of tumour development, or that they, as an expression of intrinsic tumour heterogeneity, may develop in different directions from the start.

Axilla↗

PubMed1992

Syntactic structure analysis of the arrangement of nuclei in dysplastic epithelium of colorectal adenomatous polyps.

In search of new objective classifiers of the degree of dysplasia in colorectal adenomatous polyps, we conducted syntactic structure analysis on hematoxylin-eosin-stained tissue sections of 59 colorectal adenomas. The adenomas were subjectively graded as showing mild (n = 20), moderate (n = 20) or severe (n = 19) dysplasia in a double-blind examination by two pathologists. Using an interactive video-overlay measuring system, a minimum spanning tree was computed in 10 fields per specimen according to a strict measurement protocol. From each minimum spanning tree, such features as total line length, length of line segments, total number of points and number of points with one, two, three or four neighbors were derived. Simple descriptive statistics of these minimum spanning tree features were used to analyze differences between the three grades of dysplasia. Univariate analysis indicated that most of the variables used were suitable for discriminating between mild and moderate as well as between mild and severe grades of dysplasia. Only median minimum line length also showed significant differences between moderate and severe dysplasia. By means of a jackknifed stepwise discriminant analysis, an overall correct classification of mild versus moderate and severe dysplasia of 81.4% was achieved. It is concluded that syntactic structure analysis may have additional value in describing, in an objective and rapid way, the morphologic changes of dysplasia in colorectal adenomatous polyps.

Adenoma↗

PubMed1990

[Quantitative methods in diagnostic pathology].

The classical pathological diagnosis is of decisive importance for adequate therapy choice. Unfortunately, inconsistency in judgement of the same case and disagreement in diagnosis between different pathologists can be pronounced. Nevertheless, techniques of quantitative pathology largely improve the reliability of diagnosis because of their, in principle, high objectivity and reproducibility. Besides stereology, morphometry and flow cytometry recently also digital image processing, three dimensional laser scan microscopy and multimedial integrated image-database expert systems are becoming increasingly applicated. However, to gain maximum profit of these quantitative methods, sufficient measurement error handling is indispensable. In addition, concepts of standardisation and ongoing quality control should be available to assure confident measurements as a valuable aid in the diagnostic process.

Cytodiagnosis↗

PubMed1990

Computer assisted efficiency testing of different sampling methods for selective nuclear graphic tablet morphometry.

Selective nuclear graphic tablet morphometry is widely employed as a useful tool in quantitative pathological assessments. The value of such a measuring system is strongly determined by the sampling rule that has to ensure high measurement precision with minimal effort. Therefore, the efficiency of four different random sampling methods (i.e., the pure "random," "zone," "at convenience," and "raster" methods) was tested by means of computer simulated sampling in nuclear study populations derived from histological sections of three endometrial hyperplasias and nine endometrial carcinomas. The 12 nuclear study populations each consisted of 1000 intact nuclei that were systematically measured within demarcated measurement fields by an experienced morphometrist. To attain an arbitrarily chosen measurement precision of 2.5% the computer simulations showed that the random and the raster methods required much smaller sample sizes than the zone and at convenience methods. By using the random and raster methods for assessment of the nuclear area, a maximal sample size of 200 nuclei was necessary, whereas the zone and at convenience methods mostly required more than 200 nuclei. For features such as the perimeter, longest axis, shortest axis, and two shape factors (form-PE and roundness), and the same level of precision, the sample size could be considerably smaller. The differences in efficiency can be explained by the existence of clustering and gradients in the value distribution of a nuclear feature within the measurement field. In contrast to the zone and at convenience methods, the random and raster methods sample nuclei from the entire measurement field and thus do not limit sampling to only a few larger areas within that field. Consequently, the latter two sampling methods cope better with an uneven spatial distribution in the magnitude of a nuclear feature and can thereby help to keep the measurement reproducibility high.

Analysis of Variance↗

PubMed1988

Analysis of measuring system parameters that influence reproducibility of morphometric assessments with a graphic tablet.

The morphometric analysis of nuclear characteristics by means of a graphic tablet is, in principle, objective and highly reproducible. However, a recent study found considerable variation in the morphometric assessments, which was in contrast to the findings of others. The way in which measurements were performed differed in these studies. Therefore, measuring system factors that can potentially influence the quantitative results were analyzed systematically. One observer, experienced in microscopic analysis and working with a commercially available graphic tablet, conducted all the measurements, thus excluding interobserver variation. The tracing speed, localization (on the graphic tablet), magnification, pen and cursor usage, shape, and orientation on the graphic tablet were analyzed. A nomogram was developed for cursor application that indicates the relation between "projected" particle size, tracing speed, and required coefficient of variation (CV). When the influence of these factors is taken into account, a measuring system can be tuned optimally. With such a regimen, the CV can be kept below 1.5%. Our results show that in the assessment of morphometric features with the use of a graphic tablet, errors due to the measuring system can be virtually eliminated.

Computer Graphics↗