Biomedical subjects

R Montironi

Publications and source records attributed to R Montironi.

At least 91 records · Page 5Linked to original sources

PubMed1998

Mitogen-activated protein kinases and apoptosis in PIN.

Mitogen-activated protein (MAP) kinases are key elements of the signalling systems needed to transduce different extracellular messages into cellular responses. At least three parallel MAP kinase pathways have been identified: one, stimulated by serum and growth factors to activate extracellular signal-regulated protein kinases (ERKs) by dual tyrosine and threonine phosphorylation, triggers cell proliferation or differentiation; the other two, induced by a variety of cellular stresses to activate c-jun N-terminal kinases (JNKs) and reactivating kinase (p38/RK), result in growth arrest and induction of apoptosis. Mitogen-activated protein kinase phosphatases (MKPs) inactivate MAP kinases through dephosphorylation and, thus, can modulate the MAP kinase pathways. Expression of JNK-1, ERK-1, p38/RK and MKP-1 proteins was investigated by immunohistochemistry and expression of MKP-1 mRNA by in situ hybridisation in 50 cases of high-grade prostatic intraepithelial neoplasia (PIN), thought to represent the precursor of prostate cancer. The frequency of apoptotic cells was also determined in these cases. Overexpression of the three MAP kinases and MKP-1 mRNA was found in all cases of high-grade PIN compared with normal prostate. Immunoreactivity for MKP-1 protein was found to be as intense as in normal glands in 30% and weaker in 56% of the PIN cases. Fourteen per cent of PIN cases did not stain with MKP-1 antibody. The proportion of apoptosis was significantly higher (P < 0.008) in PIN lesions that did not express MKP-1 protein than in those that did. These results are consistent with our previous demonstration of preferential inhibition of the apoptosis-related kinases by MKP-1 and further support the contention that MKP-1, even in PIN, may shift the balance existing between cell proliferation and death. When expressed, it may inhibiting those pathways that lead to apoptosis.

Adenocarcinoma↗

PubMed1998

Color Doppler sonography patterns related to histological findings in Graves' disease.

The aim of this work was to correlate color duplex sonography (CDS) patterns and thyroid histology in hyperthyroid Graves' disease (GD) patients. Sixteen patients with relapsed GD were studied. Before starting a new cycle of medical therapy with methimazole in decreasing doses for 3 to 6 months (baseline study), the patients underwent functional, autoimmune, and CDS studies. The same studies were carried out again just before surgery (presurgical study) after medical therapy had produced a normalization of thyroid hormone serum levels. The thyroid glands were histologically examined and their patterns were compared with CDS patterns. Thirty-three normal subjects were used as a control group. At baseline, 6 patients (group I) had intraparenchymal homogeneous vascular color spots or diffusely distributed over the parenchyma lobe or in areas alternating with avascular zones (CDS-A pattern). In 8 patients (group II) the thyroid had vascular bands with avascular or poorly vascularized parenchymal areas (CDS-B pattern). In 2 patients, the 2 patterns were present in the same thyroid (A-B pattern or mixed pattern). In these 2 patients the histological aspects were more similar to the CDS-B pattern than the CDS-A pattern. The 2 groups of patients differed in the velocity of systolic peak (VP) that was significantly higher in group I than in group II. In the presurgical study, no changes relative to CDS patterns were observed in patient groups I and II. The VP did not show any appreciable modifications in either group of patients. The thyrotropin-stimulating antibodies (TRAb) returned to normal levels in group II, but not in group I. The 2 CDS patterns, observed in the baseline study, were histologically characterized either by a richly vascularized parenchyma with prevalent endothelial hyperplasia (parenchymatous goiter, CDS-A) or by fibrotic septation with prevalent vascular intimal hyperplasia (CDS-B). In conclusion, this CDS study in GD patients showed 2 distinct vascular patterns. The thyroid glands were histologically characterized by either a richly capillary vascularized parenchyma (parenchymatous goiter, CDS-A aspect) or by fibrotic septation with prevalent intraseptal arteriolar-like hyperplasia (fibrous goiter, CDS-B aspect). Such differences may be secondary to a different duration of hyperthyroidism and/or intensity of TRAb thyroid stimulation.

Adult↗

PubMed1998

Pathological changes in prostate lesions after androgen manipulation.

The number of newly diagnosed cases of prostate cancer has doubled in the past four years because of the aging of the population coupled with growing awareness of the importance of early detection. The issues of clinical understaging and resection limit positivity have led to the development of novel management practices, including neoadjuvant hormonal treatment, which aims to downstage the primary tumour and decrease the positive margin rate before definitive localised treatment (radical prostatectomy or definitive radiation treatment (neoadjuvant)). There is conflicting evidence regarding pathological downstaging, with some studies suggesting benefit and others no benefit of androgen manipulation before radical prostatectomy. The problem might be related to incomplete sampling of the prostates and difficulties associated with the pathological interpretation of morphological changes. The least controversial aspect of neoadjuvant treatment is its impact on surgical margins. Most series have shown that neoadjuvant treatment in clinical T2 tumours is associated with a 20-25% decrease in positive margins in radical prostatectomy specimens. In patients with clinical T3 tumours, the effects of neoadjuvant treatment on positive margins are less clear. Even if some early significant advantages can be observed following hormonal treatment this may not alter the metastatic spread and overall survival rate. Only long term follow up studies evaluating biological and clinical failures, time to progression, and survival will allow definitive conclusions from this approach.

Adenocarcinoma↗

PubMed1998

Apoptosis in prostatic adenocarcinoma following complete androgen ablation.

OBJECTIVE: To analyze the cell death phenomenon in prostate cancer following complete androgen ablation. METHODS: The frequency and location of apoptotic bodies (ABs) were evaluated in haematoxylin and eosin stained sections of radical prostatectomy specimens from patients with invasive prostatic adenocarcinoma treated with neo-adjuvant endocrine combination therapy for 3 months before surgery. The results were compared with an untreated age- and stage-matched control group. RESULTS: Both in treated and untreated prostate tissue the AB frequency increased from normal prostate, through prostatic intraepithelial neoplasia, up to prostatic adenocarcinoma. The main location was in the cell layers adjacent to the stroma, their frequency decreasing towards the lumen. The frequency of ABs was higher in the treated prostate glands than in the untreated groups. The relative increase of the AB frequency in treated carcinomas as compared with untreated ones was lowest in tumours with a solid pattern, intermediate in the cribriform, and highest in the acinar pattern. CONCLUSIONS: Complete androgen ablation induces involution of prostate tissue mainly through the enhancement of apoptosis. This type of cell death is thought to play a major role and might be linked to specific changes in signal transduction mechanisms in response to hormonal withdrawal.

Adenocarcinoma↗

PubMed1998

Leuprorelin 1-month depot as neoadjuvant therapy for prostate cancer. Takeda NHT Italian Group.

In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to radical prostatectomy has been largely debated and investigated in randomized multicenter trials as well as in large single-institution studies. We have initiated a prospective randomized comparative trial with parallel groups in patients with clinically limited disease to contribute to the clarification of the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus cyproterone acetate in 'maintaining' the stage of the disease; to reduce the percentage of pathological overstaging, and mainly to accurately assess the pathological modifications induced by NHT. The present paper is an interim report of the results.

Adenocarcinoma↗

PubMed1998

Prostatic intraepithelial neoplasia and prostate cancer: analytical evaluation.

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.

Journal Article↗

PubMed1998

Machine vision in the detection of prostate lesions in histologic sections.

OBJECTIVE: To explore the utility of N-gram encoding for the automated detection and delineation of regions of histologic abnormality in tissue sections of prostate. STUDY DESIGN: Digitized imagery of tissue sections from normal prostate glandular tissue, stroma and regions of well- and poorly differentiated lesions was recorded and successively subdivided into square subregions of 256 x 256 to 16 x 16 pixels. N-grams of N = 2 to N = 6 were computed, with each element assuming a value representing an optical density interval 0.30 units wide, covering the range from optical density = 0.0 to 1.80. Then, from a large database, prototype frequency histograms of the different N-grams were established. For each subregion the Euclidean distances to the different prototype histograms were computed and defined as "distance to prototype" features. Standard discriminant analyses and a nonparametric classifier were used to assign subregions to the different tissue categories. RESULTS: Classification of subregions was achieved for most discrimination tasks at a correct recognition rate ranging from 85% to 100% on both training set and test set data, with a few exceptions. N-grams of N > 4 had considerable discriminatory power. CONCLUSION: N-gram encoding has the potential to provide highly discriminating, texture-based characterization of subregions of digitized imagery of prostate lesions and may be very useful in the development of decision procedures for the automated detection of prostate lesions by a machine vision system.

Algorithms↗

PubMed1998

Statistical histometry of the basal cell/secretory cell bilayer in prostatic intraepithelial neoplasia.

OBJECTIVE: To delineate the sampling requirements for a histometric assessment of progression in low grade and high grade prostatic intraepithelial neoplasia (PIN) lesions. STUDY DESIGN: Images of whole glands from normal prostates, low grade PIN lesions and high grade PIN lesions were digitized. The images were processed by a machine vision system and automatically segmented, and a number of histometric characteristics descriptive of the disruption of the basal cell layer were extracted. Next, high-resolution images of secretory cell nuclei still facing or no longer facing intact segments of the basal cell layer were recorded and karyometrically analyzed. RESULTS: For the characterization of an individual lesion a minimum of 20-30 glands should be analyzed to provide an estimate of a progression index. Then, a change in progression, or due to regression, of approximately 16% can be documented. The disruption of the basal cell layer is accompanied by statistically highly significant changes in the chromatin texture and spatial distribution in secretory cell nuclei no longer facing an intact segment of that layer. CONCLUSION: Automated histometry by machine vision can provide valuable quantitative data for diagnostic assessment and for monitoring the efficacy of chemopreventive treatment.

Analysis of Variance↗

PubMed1998

Nuclear chromatin texture in prostatic lesions. I. PIN and adenocarcinoma.

OBJECTIVE: To document changes in the chromatin pattern in secretory cell nuclei from prostates with prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. STUDY DESIGN: High-resolution images of nuclei were recorded, and a set of features descriptive of the chromatin texture and spatial distribution was computed. From this data set, features undergoing a monotonic trend of progression were selected and plotted to reveal trends in lesion progression. RESULTS: The nuclear chromatin in secretory cells in prostates with either PIN or malignant adenocarcinoma undergoes distinct and statistically significant changes in its texture and spatial distribution. Two trends of progressive change were observed. First, the values of a number of features descriptive of the clumpiness of the chromatin increase from values found in normal prostates to those recorded for nuclei from low grade to high grade PIN lesions. The second trend is a decrease in the values of the same features from those found in nuclei from high grade PIN still facing an intact basal cell layer to those no longer facing such a layer. This may be the first detectable step in progression towards development of a malignant lesion. There is a further decrease in nuclei in glands immediately adjacent to adenocarcinoma and in malignant lesions themselves. CONCLUSION: The described changes may lend themselves to the monitoring of lesion progression or of response to treatment or to chemopreventive intervention.

Adenocarcinoma↗

PubMed1998

Nuclear chromatin texture in prostatic lesions. II. PIN and malignancy associated changes.

OBJECTIVE: The objective of this study was to identify and document prostatic intraepithelial neoplasia (PIN) and malignancy associated changes in secretory cell nuclei from visually normal appearing tissue regions of prostates harboring PIN or adenocarcinoma. STUDY DESIGN: High-resolution digitized images of nuclei were recorded in histologically normal appearing tissue regions at defined distances from the margin of PIN or malignant lesions. Features descriptive of nuclear chromatin texture were computed and used to derive a discriminant function score for each nucleus. RESULTS: Secretory cell nuclei in prostates harboring either PIN or adenocarcinoma were shown to have statistically significantly different chromatin texture from secretory cell nuclei recorded in prostates free from any such lesion. The expression of PIN or malignancy associated changes was documented for distances up to 10 mm from the margin of a lesion. CONCLUSION: The finding of characteristic changes in nuclear chromatin texture of nuclei from histologically normal appearing tissue in prostates with PIN or adenocarcinoma offers the potential for higher sensitivity of detection of such lesions and for earlier detection of changes potentially preceding the development of clinically significant disease.

Cell Nucleus↗

PubMed1998

Chromatin texture signatures in nuclei from prostate lesions.

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.

Adenocarcinoma↗

PubMed1998

Case diagnosis as positive identification in prostatic neoplasia.

OBJECTIVE: To apply a distance measure and Bayesian belief network-based methodology to the positive identification of case diagnosis in prostatic neoplasia. STUDY DESIGN: Eight morphologic and cellular features were analyzed in 20 cases of normal prostate, 20 of low grade prostatic intraepithelial neoplasia (PIN), 20 of high grade PIN, 20 of prostatic adenocarcinoma with a cribriform pattern and 20 of prostatic adenocarcinoma with an acinar pattern. The diagnostic distance was evaluated to measure the "extent" to which the feature outcomes of the individual cases differed from the expected profile of outcomes in typical cases of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. Belief values were evaluated with a Bayesian belief network (BBN). RESULTS: A bivariate representation of the cumulative absolute diagnostic distances of all the cases from the prototypes of normal prostate and cribriform adenocarcinoma was made. Three separate groups of cases were observed, corresponding to normal prostate, low grade PIN and cribriform adenocarcinoma. An additional group was formed by the cases of high grade PIN and acinar adenocarcinoma--i.e., there was complete overlap between the diagnostic distance values of cases belonging to these two categories. However, these cases showed differences in clue outcomes. To explore the contribution of such observations to case identification, a bivariate representation of the diagnostic distances from high grade PIN and acinar adenocarcinoma was made. The cases then formed five separate groups corresponding to the five diagnostic categories. When the individual cases were considered, their shortest distance was from the prototype of the category into which they were originally diagnosed. The BBN gave these diagnostic categories the highest belief values. CONCLUSION: The combined evaluation of diagnostic distance and belief represents an identification procedure. The numeric value of certainty characterizes individual cases according to the level of progression from PIN toward cancer.

Bayes Theorem↗

PubMed1998

Automated histometry in quantitative prostate pathology.

OBJECTIVE: To review progress on the development of machine vision and image understanding in prostate tissue histology and to discuss the problems and opportunities afforded to pathology through the use of these techniques. STUDY DESIGN: A variety of concepts in machine vision are explored, and methodologies are described that have been developed to deal with the complexities of histologic imagery. The theory of human vision and its impact on machine vision are discussed. Software has been specifically developed for the analysis of prostate histology, allowing accurate gland segmentation, basal cell identification and measurement of vascularization within lesions. RESULTS: Image interpretation can be achieved using knowledge-based image analysis and the application of local object-oriented processing. This successfully allows an automated quantitative analysis of histologic morphology in the diagnosis of prostate intraepithelial neoplasia and invasive prostatic cancer. The use of low-power image scanning, based on textural or n-gram mapping, permits the development of fully automated devices for the rapid detection of tissue abnormalities. High-power, knowledge-guided scene segmentation can be carried out for the quantitative analysis of cellular features and the objective grading of the lesion. CONCLUSION: Automated tissue section scanning and image interpretation is now possible and holds much promise in prostate pathology and other diagnostically demanding areas. Issues of standardization still need to be addressed, but the development of such systems will undoubtedly enhance our diagnostic capabilities through the automation of time-consuming procedures and the quantitative evaluation of disease processes.

Humans↗

PubMed1997

Computerized scene segmentation for the discrimination of architectural features in ductal proliferative lesions of the breast.

The distinction between ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS) still remains a problem in the histological diagnosis of non-invasive breast lesions. In this study, a method was developed for the automatic segmentation and quantitative analysis of breast ducts using knowledge-guided machine vision. This permitted duct profiles and intraduct lumina to be identified and their shape, size, and number computed. These were used to derive measures of duct cribriformity and architectural complexity which were examined as an objective tool in the characterization of duct pattern in proliferative lesions. A total of 215 images of ducts were digitally captured from 22 cases of DCIS and 21 cases of DH diagnosed independently by two pathologists. The cribriformity index proved to be a useful measure of duct architecture, showing a nosotonic increase with increasing duct complexity. The number of lumins also increased with increasing overgrowth of ductal epithelium until the duct was filled. Discriminant analysis of the duct characteristics for benign and malignant groups selected the lumen area/duct area ratio and the duct area as significant discriminatory variables and they were combined into a discriminant function. Of the lumens features, the mean area of the lumen and the polar average (mean of the distribution of the number of events with an increasing spiral from the centre of the duct) were combined into a second discriminant function. Plotting cases against these two functions provided good separation of DH and DCIS groups, with correct classification estimated on the training sample as being over 80 per cent. With an increasing incidence of complex proliferative lesions arising from mammography, the ability to diagnose these lesions correctly is more important than ever. The use of expert system-guided machine vision facilitates the quantitative evaluation of breast duct architecture; along with established histological and cytological criteria, it is hoped that this will lead to a more objective means of diagnosis and disease classification.

Aged↗

PubMed1997

Automated location of dysplastic fields in colorectal histology using image texture analysis.

Automation in histopathology is an attractive concept and recent advances in the application of computerized expert systems and machine vision have made automated image analysis of histological images possible. Systems capable of complete automation not only require the ability to segment tissue features and grade histological abnormalities, but, must also be capable of locating diagnostically useful areas from within complex histological scenes. This is the first stage of the diagnostic process. The object of this study was to develop criteria for the automatic identification of focal areas of colorectal dysplasia from a background of histologically normal tissue. Fields of view representing normal colorectal mucosa (n = 120) and dysplastic mucosa (n = 120) were digitally captured and subjected to image texture analysis. Two features were selected as being the most important in the discrimination of normal and adenomatous colorectal mucosa. The first was a feature of the co-occurrence matrix and the second was the number of low optical density pixels in the image. A linear classification rule defined using these two features was capable of correctly classifying 86 per cent of a series of training images into their correct groups. In addition, large histological scenes were digitally captured, split into their component images, analysed according to texture, and classified as normal or abnormal using the previously defined classification rule. Maps of the histological scenes were constructed and in most cases, dysplastic colorectal mucosa was correctly identified on the basis of image texture: 83 per cent of test images were correctly classified. This study demonstrates that abnormalities in low-power tissue morphology can be identified using quantitative image analysis. The identification of diagnostically useful fields advances the potential of automated systems in histopathology: these regions could than be scrutinized at high power using knowledge-guided image segmentation for disease grading. Systems of this kind have the potential to provide objectivity, unbiased sampling, and valuable diagnostic decision support.

Adenomatous Polyps↗

PubMed1997

Subtle changes in benign tissue adjacent to prostate neoplasia detected with a Bayesian belief network.

The aim of this paper was to test the usefulness of a Bayesian belief network (BBN) as a decision support system in the uncertainty assessment of benign prostatic tissue, either associated or not with inflammation or adjacent to prostatic adenocarcinoma (PAC) or prostatic intraepithelial neoplasia (PIN). A shallow network was used with eight first-level descendant nodes for the diagnostic clues, each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives. One diagnostic evidence node was based on the tissue architecture and the others were based on cell features. The efficacy of the network was tested on a series of 45 simple prostatectomy specimens, subdivided as follows; benign prostatic tissue not associated with other diseases (15 cases), associated with acute and/or chronic inflammation (15 cases), and adjacent to accidentally discovered PAC or PIN (15 cases). The highest belief values for the diagnostic alternative normal prostate (NP) were obtained in the 15 cases not associated with other diseases, the mean value being 0.996. The 15 cases evaluated in areas with inflammation showed the lowest belief values for NP (mean 0.774). For the 15 cases evaluated in specimens with PAC or PIN, the belief values for NP were intermediate between those from normal prostatic tissue associated with inflammation and those not associated (mean 0.925). Moreover, it was found that subtle changes were also present at a certain distance from the tumour. In conclusion, the network can be used as a decision support system to differentiate with high certainty benign prostate adjacent to PAC or PIN from benign prostatic tissue either associated or not with inflammation. The subtle morphological alteration detected with the BBN may be considered malignancy-associated changes.

Adenocarcinoma↗

PubMed1997

Evaluating radical prostatectomy specimens: therapeutic and prognostic importance.

The pathologic staging of prostate cancer involves determination of the anatomic extent and burden of tumor based on the best available data. Proper examination of radical prostatectomy specimens is critical in determining cancer stage, stratifying patient need for adjuvant treatment, and prediction of patient outcome. Differences exist in methods of handling and sampling specimens, although publication of practice protocols in recent years has led to convergence of opinion. In this report, we evaluate the current aspects of pathologic staging of prostate cancer and assessment of prostatectomy specimens. Recent international agreement on pathologic staging of prostate cancer should allow valid comparisons of surgical treatment from different institutions. The vanishing cancer phenomenon is also briefly discussed.

Carcinoma↗

PubMed1997

Prostate pathology case study seminar.

Great strides have been made in the past decade in our understanding of the pathology of the prostate. Diagnostic criteria have been proposed, debated, and refined for a number of entities, including prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, basal cell proliferations, postatrophic hyperplasia, verumontanum mucosal gland hyperplasia, and numerous new variants of prostatic adenocarcinoma such as ductal adenocarcinoma, mucinous carcinoma, signet ring cell carcinoma, and lymphoepithelioma-like carcinoma. This report presents a series of case studies in prostate pathology which illustrate some of the contemporary issues which confront the pathologist and urologist.

Adenocarcinoma↗