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Biomedical subjects

B Nordin

Publications and source records attributed to B Nordin.

At least 19 recordsLinked to original sources

Histology corresponding to mildly dyskaryotic smears--a study of 190 laser cone biopsied patients.

OBJECTIVES: The aim of the study was to evaluate the histological outcome of laser ring biopsies in patients with one or more smears showing cytological mild dyskaryosis where punch biopsies were not performed. The possibilities of predicting histological findings of CIN 2 and CIN 3 were analyzed. METHODS: The study comprised 190 laser ring biopsied patients with mildly dyskaryotic smears. Eighty-five patients were excluded from the initial 275 because of up- and downgrading of smears. Conization specimens and smears were reviewed by an experienced histopathologist and two experienced cytotechnicians. The histological findings were correlated to smear findings. RESULTS: Histologically, CIN 2 was found in 60 and CIN 3 in 45 patients (31 and 24%, respectively). The incidence of histological CIN 3 was higher in those with two or more mildly dyskaryotic smears and in those dyskaryotic smears lacking koilocytic change. Mildly dyskaryotic smears without endocervical cells indicated higher incidence of histological CIN 3. The fact that 36 of 96 CIN 2 and 3 lesions (38%) involved only 3 mm or less of the mucosa might be one important explanation for the absence of representative cells in the corresponding smears. CONCLUSIONS: Our study has shown that a mildly dyskaryotic smear is a strong indicator of CIN 2-3 histologically, especially in those cases without koilocytic cells and in those with repeatedly abnormal smears. The importance of inadequate sampling is indicated by higher incidence of histological CIN 3 in those with less than optimal smears. These findings are some of the factors to be taken into account when planning treatment strategies for this group of patients.

Adult↗

Neo-adjuvant GnRH therapy and radical prostatectomy: effects on tumorous and benign tissue volumes - a morphometric study.

UNLABELLED: The effect on tumour and prostate volumes of a 3-month course of neo-adjuvant hormone therapy was studied using computerised planimetry on serially sectioned specimens obtained by radical prostatectomy. Fifty-four specimens from patients not receiving pre-treatment were compared to 38 specimens from patients given the gonadotropin-releasing hormone (GnRH) analogue triptorelin for 3 months before the operation. Glandular volume and volume of the index tumour was determined. To determine the position of the index tumour within the gland, the centre of mass of the tumour was identified and the distance to the gland margin calculated. This value (M1) represents the sum of the tumour radius and the various amounts of normal tissue. The amount of surrounding tissue could be approximated by correlating M1 to the corresponding tumour volume. RESULTS: The two groups differed significantly in total gland volumes, but not in tumour volumes. M1 was strongly correlated to the tumour volume in the treatment group (r = 0.73), whereas in the control group the correlation was found to be significantly weaker (r = 0.44), indicating that there was less tissue surrounding the tumour in the pre-treated group. In a multiple regression analysis of all 92 patients, index tumour volume was found to be associated with total gland volume, DNA ploidy pattern, tumour grade but not whether or not pre-treatment was given. This study found that the volumes of the single largest tumour focus were not significantly affected by hormonal pre-treatment, and that "the prostate condenses around the tumour rather than that the tumour shrinks back into the prostate". However, the precise relationship between tumour epithelial volume and stroma with or without neo-adjuvant hormonal pre-treatment remains to be clarified.

Gonadotropin-Releasing Hormone↗

Morphometric studies of intra-prostatic volume relationships in localized prostatic cancer.

OBJECTIVES: To further characterize patterns of tumour growth and the distribution of markers for the aggressiveness of prostate cancer by assessing the relationships among the volume of the 'index' tumour and that of the remaining foci, with pathological (pT) stage, histological grade and DNA ploidy, and with the amount of low- and high-grade prostatic intraepithelial neoplasia (PIN). MATERIALS AND METHODS: Eighty-eight step-sectioned total prostatectomy specimens were analysed. The Gleason score, tumour stage and DNA ploidy (by flow cytometry) of multiple samples were determined. Tumour and PIN areas were outlined and their volumes estimated by computerized planimetry. RESULTS: The pT stage, Gleason sum and DNA nondiploidy increased, and PIN volumes decreased, with increasing volume of the index tumour focus (P < 0.01), but did not differ significantly between uni- and multifocal tumours. However, PIN volumes were significantly larger in multifocal cases with an index tumour volume of > 3 mL than in unifocal tumours > 3 mL (P < 0.05). Small volume, unifocal tumours had little PIN. The most malignant features of each case were always represented in the index tumour but not generally in the remaining foci. CONCLUSIONS: The volume distribution, related to multicentricity and its concomitant PIN volumes, indicates that large index tumours, uni- or multifocal, of medium or high grade, are associated with low PIN volumes. However, multifocal medium- and high-grade tumours with small index tumour volumes have higher PIN volumes. Small, single tumours are of low-grade and may represent the slowly progressing cancers possibly resembling those found in autopsy studies.

Aged↗

A new method for segmentation of colour images applied to immunohistochemically stained cell nuclei.

A new method for segmenting images of immunohistochemically stained cell nuclei is presented. The aim is to distinguish between cell nuclei with a positive staining reaction and other cell nuclei, and to make it possible to quantify the reaction. First, a new supervised algorithm for creating a pixel classifier is applied to an image that is typical for the sample. The training phase of the classifier is very user friendly since only a few typical pixels for each class need to be selected. The classifier is robust in that it is non-parametric and has a built-in metric that adapts to the colour space. After the training the classifier can be applied to all images from the same staining session. Then, all pixels classified as belonging to nuclei of cells are grouped into individual nuclei through a watershed segmentation and connected component labelling algorithm. This algorithm also separates touching nuclei. Finally, the nuclei are classified according to their fraction of positive pixels.

Algorithms↗

Cervex-Brush vs. spatula and Cytobrush. A cytohistologic evaluation.

OBJECTIVE: To compare the efficacy of two cervical smear instruments, Cervex-Brush and spatula plus Cytobrush. STUDY DESIGN: Cervical smears were taken before laser ring biopsies in 213 women, who were randomized for the Cervex-Brush or spatula plus Cytobrush (S+C). The cytologic diagnosis was compared to the histologic diagnosis after laser ring biopsy. RESULTS: The correlation between cytology and histology showed comparable concordance (54% and 42%) for the two devices. In 130 (74 with Cervex-Brush and 56 S+C) patients, histology revealed moderate dysplasia or more advanced lesions. Those cases were further analyzed for smear failures. Negative smears were found in 13 cases (10 in the Cervex-Brush and 3 in the S+C group). This difference in favor of S+C was not, however, statistically significant. Significantly more false negative smears were found when endocervical cells were absent and in patients 30-39 years of age. CONCLUSION: Modern sampling devices, such as the Cervex-Brush and S+C, seem to be equally efficient in obtaining dysplastic squamous cells. Other factors of importance for nonrepresentative cervical smears should be studied in order to improve efficacy.

Adult↗

MUSE--a new tool for interactive image analysis and segmentation based on multivariate statistics.

MUSE--a new software tool for the interactive exploration of multivariate images and the development of image segmentation methods has been designed, implemented, and tested in a number of real application projects. The multivariate statistical classification and projection methods in MUSE can be used not only to analyze multispectral images but also, in special cases, multitemporal images and volume images. Additionally MUSE can be applied to normal greyscale images provided they are made multivariate through an initial processing step. This step may consist in the application of filters designed to enhance any existing texture differences between different regions in the images. MUSE has been successfully applied to medical images (color photographs, MR, PET, SPECT) as well as to satellite images (Landsat TM).

Diagnostic Imaging↗

Standardized in vitro mapping with multiple core biopsies of total prostatectomy specimens: localization and prediction of tumour volume and grade.

OBJECTIVE: To analyse the ability of systematic core biopsy mapping to provide prognostic information in patients with prostatic cancer. MATERIALS AND METHODS: The prostates of 60 men with prostatic cancer, stages T0d-T2, who had undergone total retropubic prostatectomy were studied. The average age of the patients was 63 years (range 49-72). Ten core biopsies (1.2 x 35 mm) were taken from the fresh specimens according to a standardized procedure. The total prostatectomy specimens were serially step-sectioned at 5 mm intervals and were assessed regarding tumour volume, grade and pT-stage. The World Health Organization (WHO) grade obtained in the mapping biopsies was compared with that in the operative specimens. Undergrading (WHO) decreased substantially by mapping biopsies, but was still present with the Gleason system. RESULTS: The volume of extracapsular tumours with extensively positive margins was significantly larger than that of intracapsular tumours (P < 0.01). In addition, the fraction of cancer obtained in the biopsies from tumours with grossly positive margins was significantly smaller than that observed in biopsies from pT2 tumours (P < 0.01). The cancer volume calculated from the result of the mapping correlated positively with the tumour volume determined by planimetry (R = 0.83). A weaker correlation was found when only the six dorsal mapping biopsies were taken into consideration (R = 0.68), but the correlation increased to R = 0.75 when the six most significant biopsies were selected with the help of a correlation matrix. Biopsies from the ventral part of the prostate were also important, to obtain an accurate assessment of the tumour fraction within the whole gland. CONCLUSION: Mapping of the prostate gland with multiple (six or more) core biopsies is necessary for preoperative assessment of tumour volume, grade and pT stage; these are all of importance when assigning patients with clinically localized prostatic cancer to prognostic classes.

Aged↗

Image analysis in cytology: DNA-histogramming versus cervical smear prescreening.

The visual inspection of cellular specimens and histological sections through a light microscope plays an important role in clinical medicine and biomedical research. The human visual system is very good at the recognition of various patterns but less efficient at quantitative assessment of these patterns. Some samples are prepared in great numbers, most notably the screening for cervical cancer, the so-called PAP-smears, which results in hundreds of millions of samples each year, creating a tedious mass inspection task. Numerous attempts have been made over the last 40 years to create systems that solve these two tasks, the quantitative supplement to the human visual system and the automation of mass screening. The most difficult task, the total automation, has received the greatest attention with many large scale projects over the decades. In spite of all these efforts, still no generally accepted automated prescreening device exists on the market. The main reason for this failure is the great pattern recognition capabilities needed to distinguish between cancer cells and all other kinds of objects found in the specimens: cellular clusters, debris, degenerate cells, etc. Improved algorithms, the ever-increasing processing power of computers and progress in biochemical specimen preparation techniques make it likely that eventually useful automated prescreening systems will become available. Meanwhile, much less effort has been put into the development of interactive cell image analysis systems. Still, some such systems have been developed and put into use at thousands of laboratories worldwide. In these the human pattern recognition capability is used to select the fields and objects that are to be analysed while the computational power of the computer is used for the quantitative analysis of cellular DNA content or other relevant markers. Numerous studies have shown that the quantitative information about the distribution of cellular DNA content is of prognostic significance in many types of cancer. Several laboratories are therefore putting these techniques into routine clinical use. The more advanced systems can also study many other markers and cellular features, some known to be of clinical interest, others useful in research. The advances in computer technology are making these systems more generally available through decreasing cost, increasing computational power and improved user interfaces. We have been involved in research and development of both automated and interactive cell analysis systems during the last 20 years. Here some experiences and conclusions from this work will be presented as well as some predictions about what can be expected in the near future.

Cervix Uteri↗

Cytophotometric estimation of cell proliferation in breast cancer. Correlation to the clinical course during long-term follow-up.

Tumours from 117 patients with breast cancer operated during a 5-month period 1975-1976 were investigated by absorbance scanning cytophotometry. The relations of these data to breast cancer recurrence and death during a follow-up period of 8.5 years were analysed using Cox's proportional hazards model. When individually tested, nodal status, grade of malignancy and high rates of proliferation, as indicated by cells in S-phase, were statistically significant predictors of the clinical outcome. The risk ratio associated with S-phase decreased significantly over time from primary treatment. No significant relation was found between DNA-ploidy or tumour size and the clinical course. In the multivariate analysis, based on 76 patients, nodal status alone was a significant prognostic factor.

Adult↗

Image cytometry in malignancy grading of breast cancer. Results in a prospective study with seven years of follow-up.

A fully automated system for image cytometry is presented. In combination with a special tumor sampling procedure, the system proved able to record with high reproducibility a large number of tumor cell population descriptors of high prognostic significance in a prospective study of breast cancer. These included the degree of abnormality of DNA distribution (strongly correlated with the proliferative rate) and some descriptors of shape and texture (strongly correlated with the grading system for breast cancer suggested by the World Health Organization). While the extreme complexity of a true malignancy grading system for breast cancer is underlined, the results of this study indicate that its creation is a possibility, given sufficient effort by interdisciplinary teams using modern sophisticated analytical techniques.

Breast Neoplasms↗

A program for logistic prediction modelling.

A computer program has been developed that can be used for analysing a binary outcome variable and a set of regressors of type interval with a logistic (i.e. nonlinear) model.

Biometry↗

Histopathological systems of breast cancer classification: reproducibility and clinical significance.

The inter- and intraobserver reproducibilities of the histopathological systems of breast cancer classification suggested by the World Health Organisation (WHO), the Armed Forces Institute of Pathology (AFIP) and Ackerman have been analysed. The reproducibilities of the three classification systems were only "fair" to "moderate" and no correlation with the five-year recurrence rate was found. Our results indicate that these classification systems are without biological significance and are useless for prognosis in the individual patient. When the tumours were classified according to degree of differentiation (high, moderate, low) or graded according to WHO (which includes both differentiation and nuclear atypia), however, there was a significant correlation with the five-year recurrence rate. Yet even such "reduced" subdivisions are of no value in judging prognosis for the individual patient at the time of diagnosis; rather, they are useful only in the follow-up analysis of groups of patients.

Breast Neoplasms↗

Correlation between cytometric features and mitotic frequency in human breast carcinoma.

An evaluation of cytometric features of 142 human breast cancers was performed. Twenty-two cytometric features describing density, structure and shape were correlated with mitotic frequency and labeling index of some of the tumors and with the observed recurrence rate of the tumors within 3 years after removal of the breast. A new cytometric measure was also created by combining the four features most strongly correlated with mitotic frequency of the tumors. It was found that the variance of the nuclear area was the feature that was most strongly correlated with mitotic frequency and recurrence rate. No new cytometric measure created by combining the four features most strongly correlated with mitotic frequency, correlated as well as variance of nuclear area even though the four features were optimized by multiple regression analysis for their correlation with mitotic frequency.

Breast Neoplasms↗

A morphometric expression of differentiation in fine-needle biopsies of breast cancer.

An automated method of particle sizing in fine-needle biopsies of human breast carcinomas is described. The average size of clusters of cells aspirated from breast carcinomas was strongly correlated with cytologic differentiation of the tumors and also with the recurrence rate 3 years after mastectomy so that smaller cluster size was associated with poor differentiation and a poor prognostic outcome. It thus seems possible to express in quantitative terms the degree of differentiation of breast carcinomas.

Biopsy, Needle↗