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R Montironi

Publications and source records attributed to R Montironi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Knowledge-based image analysis in the precursors of prostatic adenocarcinoma.

OBJECTIVES: It is the objective of this study to present the use of knowledge-guided procedures in quantitative image analysis and interpretation in histopathology. METHODS: The knowledge-guided procedures were implemented in the form of N-gram encoding methods for the search and detection of areas of atypicality or abnormality in histopathologic sections; they were implemented as expert system for automated scene segmentation based on an associative network with frames at each node. The extraction of histometric features from the basal cell layer of prostatic lesions is presented as an example of automated image interpretation. RESULTS: Rapid search algorithms for lesion detection were able to identify approximately 90% of areas labelled as atypical or abnormal by visual assessment, in lesions of colon, prostate and breast. Automated segmentation of very complex histopathologic imagery was possible with a success rate of approximately 80-90%, in sections of prostatic and colonic lesions. Histometry of the deterioration of the basal cell layer in prostatic lesions provided a monotonic trend curve suitable for the measurement of progression or regression. CONCLUSIONS: Knowledge-guided procedures bring external information, not offered by the imagery itself, to bear on image processing and image analytic methods. This has enabled automated analysis and interpretation of very complex imagery, such as from cribriform glands, resulting in quantitative diagnostic information.

Adenocarcinoma↗
PubMed1996

Androgen-deprived prostate adenocarcinoma: evaluation of treatment-related changes versus no distinctive treatment effect with a Bayesian belief network. A methodological approach.

OBJECTIVE: To develop and test a Bayesian belief network (BBN) for the identification of prostatic adenocarcinomas (PACs) with combination endocrine therapy (CET) changes from PACs with poor to no treatment CET effect and from untreated PACs. METHODS: A network was designed with a decision node containing three diagnostic alternatives (PAC with CET effect, PAC with poor to no treatment effect, and untreated PAC) and seven first-level evidence nodes for the diagnostic features: nuclear enlargement; frequency of prominent nucleoli; cell cytoplasm vacuolization; shrunken acini; individual infiltrating tumor cells; WHO prostate cancer pattern recognition, and amount of interstitial tissue stroma. Three prototype cases, one for each diagnostic alternative, were used to develop the BBN. The BBN performance was then evaluated in 40 prostatectomies for PAC, consisting of 20 CET treated and 20 untreated cases. RESULTS: The results obtained with the three prototypes showed that the network can identify the diagnostic alternatives with certainty when seven features are polled. When the performance was evaluated in the 40 PACs, the belief values were 1.0 or close to it in most of the cases (the value range is 0.0-1.0; the closer to 1.0, the greater the belief). Moreover, the BBN allowed an identification with high certainty of PACs with treatment-related changes from those either with poor to no treatment effect or untreated. CONCLUSIONS: A BBN for the evaluation of androgen-deprived PAC offers a descriptive classifier which is readily implemented and allows the use of descriptive, linguistic terms.

Adenocarcinoma↗
PubMed1996

Effects of neoadjuvant androgen deprivation therapy on prostatic cancer.

OBJECTIVES: In this study, we analyzed the involutive effects of androgen deprivation therapy on normal and neoplastic prostatic tissue, to investigate whether androgen deprivation prior to radical prostatectomy could reduce the incidence of extracapsular extension, positive margins, positive seminal vesicles and positive lymph nodes in patients with prostatic carcinoma. METHODS: We performed neoadjuvant androgen deprivation therapy (NADT) in 41 patients cT2N0M0 and in 21 patients cT3N0M0. Criteria to evaluate the effectiveness of NADT included prostate volume, tumor volume, serum prostate-specific antigen (PSA), staging, grading, histological modifications of the tumor, and evaluation of indices of cellular proliferation. RESULTS: We observed a decrease in prostate and tumor volume, as well as serum PSA; a down-staging effect was observed in 14.51% of cases. Evaluation of proliferating-cell nuclear antigen (PCNA) revealed a decrease of proliferative activity in treated prostatic carcinoma. The histological modifications after neoadjuvant therapy consisted of cellular necrosis with apoptotic phenomena, dense chromatin without nucleoli, absence of mitosis, inflammatory infiltrate, and interstitial fibrosis. Regressive aspects similar to those of neoplastic cells were observed in prostatic intraepithelial neoplasia. CONCLUSION: Our assessment of the biologic effects of NADT on tumoral activity of prostatic carcinoma led us to conclude that NADT can reduce the cellular proliferation of neoplastic cells.

Adenocarcinoma↗
PubMed1996

Enhanced expression of transforming growth factor beta1 in rat thyroid hyperplasia is thyrotropin induced and time dependent.

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Animals↗
PubMed1996

Renal oncocytoma. Pathological evaluation and clinical implications.

Renal oncocytoma is a benign tumour of renal tubular origin; oncocytes are transformed epithelial cells rich in mitochondria, probably representing senescent degenerative cellular changes. Most of renal oncocytomas usually follow a benign clinical course and partial nephrectomy or enucleation has been advocated as curative. By immunohistological staining of tissue sections using monoclonal antibodies (DBA, SBA, PNA, UEA, Cytocheratine), we can suppose the histogenetic origin of renal oncocytomas from a region other than the proximal tubular epithelium, and in particular from the collecting duct epithelium. We believe that it is most important to perform flow cytometry to study the chromosomal pattern of the tumour, once intra-operative frozen sections have advanced the suspicion of renal oncocytoma; if oncocytic cells show a diploid pattern, and the tumour mass is well circumscribed and has not an excessive diameter, we favour renal sparing surgery.

Adenoma, Oxyphilic↗
PubMed1996

Knowledge-guided histometry of the basal cell layer in prostatic intraepithelial neoplasia.

OBJECTIVE: To define a procedure for the fully automated evaluation of histopathologic sections of prostatic intraepithelial neoplasia. STUDY DESIGN: The design is based on expert system-guided scene segmentation, the construction of a knowledge file and the defining of histometric measures for assessment of the basal cell layer. RESULTS: A knowledge file specifying a total of 263 entities was constructed. Of 73 multimegapixel-sized images of cribriform glands, 71 were correctly and completely processed. A histometric measure allowing precise indexing of the degree of lesion progression, based on the deterioration of the basal cell layer, was derived. CONCLUSION: The combination of image analytic and immunohistochemical procedures and fully automated processing provides a quantitative measure for evaluating prostatic intraepithelial neoplasia lesion progression and the effects of intervention.

Expert Systems↗
PubMed1996

Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). A methodologic approach.

OBJECTIVE: To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two simple prostatectomy specimens from patients with clinical diagnoses of benign prostatic hyperplasia and treated with finasteride for six months. The feasibility of PIN diagnosis and grading based on "diagnostic distance" was investigated. It is a measure of the "extent" to which the observed features are different from those of the untreated prototypes representing the following diagnostic categories: normal prostate, low and high grade PIN and prostatic adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN diagnosis and grading was dealt with by means of a Bayesian belief network (BBN). RESULTS: The distance measure values of the three PIN foci from the prototype of untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative, arbitrary units. Their distance from the two prostate cancer patterns (large acinar and cribriform) was as high as 8-10. The distance of these foci from either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4, respectively. BBN produced the highest belief values for PIN, thus confirming the morphology-based and diagnostic distance-supported diagnosis; however, the belief values were low for both grades. CONCLUSION: The results provided by BBN analyses and diagnostic distance measures support the conclusion that this methodology is applicable to assessing the efficacy of finasteride treatment of PIN.

5-alpha Reductase Inhibitors↗
PubMed1995

Prostatic intraepithelial neoplasia (PIN). Performance of Bayesian belief network for diagnosis and grading.

Prostatic intraepithelial neoplasia (PIN) diagnosis and grading are affected by uncertainties which arise from the fact that almost all knowledge of PIN histopathology is expressed in concepts, descriptive linguistic terms, and words. A Bayesian belief network (BBN) was therefore used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependences between elements in the reasoning sequence. A shallow network was used with an open-tree topology, with eight first-level descendant nodes for the diagnostic clues (evidence nodes), each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives (decision node). One of the evidence nodes was based on the tissue architecture and the others were based on cell features. The system was designed to be interactive, in that the histopathologist entered evidence into the network in the form of likelihood ratios for outcomes at each evidence node. The efficiency of the network was tested on a series of 110 prostate specimens, subdivided as follows: 22 cases of non-neoplastic prostate or benign prostatic tissue (NP), 22 PINs of low grade (PINlow), 22 PINs of high grade (PINhigh), 22 prostatic adenocarcinomas with cribriform pattern (PACcri), and 22 prostatic adenocarcinomas with large acinar pattern (PAClgac). The results obtained in the benign and malignant categories showed that the belief for the diagnostic alternatives is very high, the values being in general more than 0.8 and often close to 1.0. When considering the PIN lesions, the network classified and graded most of the cases with high certainty. However, there were some cases which showed values less than 0.8 (13 cases out of 44), thus indicating that there are situations in which the feature changes are intermediate between contiguous categories or grades. Discrepancy between morphological grading and the BBN results was observed in four out of 44 PIN cases: one PINlow was classified as PINhigh and three PINhigh were classified as PINlow. In conclusion, the network can grade PIN lesions and differentiate them from other prostate lesions with certainty. In particular, it offers a descriptive classifier which is readily implemented and which allows the use of linguistic, fuzzy variables.

Adenocarcinoma↗
PubMed1995

The significance of atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma. An update.

The term prostatic intraepithelial neoplasia (PIN) is an accepted diagnosis in pathology of the prostate. The diagnostic difference between atypical adenomatous hyperplasia (AAH) and adenosis is still under debate. A number of questions remain about the significance of grading of AAH and PIN, the biology of AAH and PIN as precursors of carcinoma, the possibility of treatment of AAH and PIN and whether AAH- and PIN-associated cancers differ from non-associated carcinoma. This paper reviews the results and discussions at the First International Consultation Meeting on Atypical Adenomatous Hyperplasia and Prostatic Intraepithelial Neoplasia and the Origins of the Prostatic Carcinomas. AAH is an architectural atypia of the prostate. The histological and cytological features of AAH are intermediate between BPH and low-grade carcinoma of the prostate. Cell kinetic findings show no distinct neoplastic pattern. AAH may be a precursor of transition zone carcinoma but the findings to date are inconclusive. Follow up studies should address whether the association of AAH and carcinoma is incidental or whether transition occurs between AAH and carcinoma. In contrast, PIN is an accepted preneoplastic lesion and the most likely precursor of the dorso-peripheral zone carcinoma. The diagnosis of high-grade PIN is clinically important, because high-grade PIN is associated with carcinoma in a high percentage of patients (38-100%). AAH- and PIN-associated cancers may not differ from other prostatic cancers. At present treatment for AAH and PIN without carcinoma is not indicated, but high-grade PIN warrants surveillance and follow up of the patient to identify a possible coexisting cancer. It must be stressed that AAH and PIN are multifocal lesions and both are age-associated.

Carcinoma↗
PubMed1995

Location of 72-kd metalloproteinase (type IV collagenase) in untreated prostatic adenocarcinoma.

The aim of the study was to investigate the location of the expression of 72-kd metalloproteinase (MMP-2) in relation to the distribution of type IV collagen in untreated prostatic adenocarcinoma (PAc). Twenty formalin-fixed, paraffin-embedded PAc cases, in which high grade prostatic intraepithelial neoplasia (PINhigh) was occasionally present, were immunohistochemically examined. Type IV collagen immunoreactivity showed the presence of a basement membrane (BM) at the epithelial-stromal junction. In cribriform and solid/trabecular PAc, the staining was focally disrupted. In acinar PAc, the BM immunostained by anti-type IV collagen was observed around the individual acini, with occasional thinning and fragmentation. Immunostaining for MMP-2 was heterogeneous in intensity and location. Cribriform and solid/trabecular PAc showed weak cytoplasmic immunostaining for MMP-2; both moderately and intensely stained cells were seen in the cell layer adjacent to the stroma; intense immunostaining was shown by small clusters of neoplastic cells or single neoplastic cells located in the stroma which also showed thinning and fragmentation of BM staining. In acinar PAc, weak cytoplasmic immunostaining for MMP-2 was seen throughout most areas of the tumours, whereas moderately and intensely stained cells were observed less frequently than in cribriform and solid/trabecular adenocarcinoma. Intense immunostaining of single or small clusters of neoplastic cells located in the stroma was rarely observed and, as for cribriform and solid/trabecular PAc, mainly located towards the periphery of the tumour nodules. BM stained by anti-type IV collagen was preserved in normal prostate and in PIN, some thinning being present in the latter. The pattern and intensity of immunoreactivity for MMP-2 in PIN was similar to that of cribriform and solid/trabecular PAc, whereas normal ducts and acini showed weak immunostaining in most of the secretory cells and moderate to strong immunoreactivity in scattered basal cells. Thus, MMP-2 appeared basically expressed in cells which lie in direct contact with the stroma. This underlined the importance of evaluating the MMP-2 location in relation to basement membrane degradation and tumour invasion.

Adenocarcinoma↗
PubMed1995

Apoptotic bodies in prostatic intraepithelial neoplasia and prostatic adenocarcinoma following total androgen ablation.

The frequency and location of apoptotic bodies (AB) were evaluated in hematoxylin- and eosin-stained sections of 12 radical prostatectomies from patients with prostatic adenocarcinoma pre-treated for 3 months with total androgen ablation. Results were compared with an untreated age-, morphology- and stage-matched control group. Treated prostates showed involutional changes, with cytoplasmic vacuolization and chromatin changes ranging from mild to severe condensation, similar to that observed in apoptosis. In treated benign prostatic epithelium, the mean number of AB was 1.64% (standard error (SE), 0.19%), 6.3 times greater than in the untreated group (mean, 0.26%; SE, 0.03%). AB were more frequent in the basal cell layer than in the lumenal cell layer, whereas in the untreated group, AB were almost exclusively found in the basal cell layer. In treated prostatic intraepithelial neoplasia (PIN present in 10 cases), the mean number of AB was 1.74% (SE, 0.04%), which was 2.56 and 2.32 times greater than in untreated low grade PIN (mean, 0.68%; SE, 0.15%) and high grade PIN (mean, 0.75%; SE, 0.11%), respectively. In treated and untreated PIN, the number of AB was greatest in the basal cell layer, less in the intermediate cell layer and lowest in the cell layer bordering the lumen. The mean number of AB in the 12 treated cancers was 1.35 times greater than in untreated cancers (1.80% [SE, 0.12%] versus 1.33% [SE, 0.32%], respectively). The number of AB in treated cases of the acinar pattern of cancer (present in 7 cancer cases) was 1.78 times greater than in untreated cases, and in treated cases of the cribriform pattern of cancer (present in four cases), the mean number of AB was 1.39 times greater than in untreated cases. The number of AB was greatest in the outermost cell layer, with progressive decrease in layers closer to the lumen. In the one treated case with solid/trabecular pattern of cancer, the number of AB was 1.08 times greater than in untreated cases. The gland lumina was rich in macrophages, sloughed secretory cells with degenerative features and AB. The number of AB in the lumina increased from normal epithelium through PIN to cancer, and was greater in treated cases than in untreated cases.

Adenocarcinoma↗
PubMed1995

Prostatic intraepithelial neoplasia. Quantitation of the basal cell layer with machine vision system.

The aim of this paper is to report on a fully automated procedure to quantify the epithelial cell components in prostatic intraepithelial neoplasia with particular emphasis on the basal cell layer (BCL). Scene segmentation was guided by a knowledge-based system of digitized images recorded from histological section immunostained against high molecular weight keratin and counterstained with hematoxylin and eosin. Scene segmentation involved two major stages. First, the system located and identified the duct and segmented the scene, resulting in "intermediate segmentation products." This stage was followed by a reconstruction process in which the segmentation products (i.e., the lumen and the darkly and lightly stained epithelial cell components) were assembled to form the microscopic structure to achieve working unity. Following this, histometric measurements were made of the reconstructed scene. Computed were the percentage of the duct contour with BCL (90%), and the number and length of gaps in the BCL (19, ranging from 10 to 90 microns). Automated analysis of the BCL is accurate and provides information not readily identified by human examination.

Basement Membrane↗
PubMed1995

Machine vision-based histometry of premalignant and malignant prostatic lesions.

The implementation of knowledge-guided control of the processing and segmentation of histopathologic images of prostatic lesions has made automated analysis and interpretation possible. To establish correspondence between histopathologic concepts, terms and diagnostic criteria, and computed histometric entities, "interpretive transforms" are introduced. Scene segmentation is controlled by an expert system following a model-based reasoning process. The expert system is structured as an associative network with frames at each node, which controls a knowledge file and a large library of image processing algorithms.

Expert Systems↗
PubMed1995

Diagnostic decision support for prostate lesions.

The diagnostic evaluation of premalignant and malignant lesions of the prostate may benefit from the application of an inference network. Used as a diagnostic decision support system, an inference network provides standardized assessment of diagnostic clues which is supported by computer graphics and comparison imagery, uncertainty management by possibility and probabilistic schemes and the systematic combination of different pieces of diagnostic evidence. This assessment results in a numeric measure of belief in the final diagnosis.

Diagnosis, Computer-Assisted↗