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R Montironi

Publications and source records attributed to R Montironi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Chromatin texture analysis of cortical adrenal gland adenomas, including incidentalomas, and adjacent normal-appearing cortical tissue.

OBJECTIVE: To describe, by morphometric and chromatin texture analysis, a series of adrenal gland lesions, including Cushing's and Conn's adenomas and incidentalomas. STUDY DESIGN: The material for the study consisted of five consecutive cases of incidentaloma, three cases of Conn's adenoma and three cases of Cushing's adenoma. Also included were five cases of adrenal carcinoma. Sections were stained according to the Feulgen procedure. Measurements were taken from the nodules and from two different zones, identified as outer and inner parts, of the normal-appearing adrenal cortex adjacent to the tumor. Data on approximately 50 nuclei were recorded for each of these three sites (tumor and outer and inner normal-appearing adrenal cortex). The nuclei were subjected to feature extraction and were analyzed by identification procedures--i.e., establishing nuclear and lesion signatures. RESULTS: The total optical density (OD) distributions of the nuclei from the normal-appearing adrenal cortex pointed to their diploid or near-diploid nature. In incidentalomas there was a very small increase in the number of nuclei, with increased total OD. In Conn's adenoma there was a noticeable but modest extension of the total OD distribution into the higher OD range. This trend continued for Cushing's adenoma. The pixel OD histograms for nuclei from normal-appearing tissue and from incidentalomas were hardly distinguishable. Starting with nuclei from Conn's adenoma, a shift toward lower pixel OD values began. The trend continued for nuclei from Cushing's adenoma and was very pronounced for nuclei from carcinoma. The nuclear signatures showed no appreciable difference between nuclei from normal-appearing cortex and from incidentaloma. Nuclei from Conn's adenoma were more similar to those from normal tissue in their signatures than nuclei from Cushing's adenoma. In fact, the nuclear signatures from Cushing's adenoma were almost identical to those of carcinoma. The lesion signatures for normal tissue, incidentaloma and Conn's adenoma confirmed the results seen in the nuclear signatures. There was a very modest increase in the number of nuclei with greater deviation from normal in incidentalomas, and the trend was more obvious in Conn's adenoma. However, in Cushing's adenoma there was a very substantial increase in the number of nuclei, with large deviations of their nuclear chromatin texture from normal. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex and highlighted the similarity between incidentalomas and adjacent normal-appearing cortex and between Cushing's adenoma and adrenal carcinoma.

Adenoma↗
PubMed2000

Prostate tissue and serum markers.

Serum prostate specific antigen (PSA) is elevated beyond the arbitrary cut-off point of 4.0 ng/ml in the majority of patients with prostate cancer (PCa). It may also be greater than 4.0 ng/ml in some benign conditions, including benign prostatic hyperplasia (BPH). Therefore, serum PSA lacks high sensitivity and specificity for PCa. This problem has been partially overcome by calculating several PSA-related indices (such as PSA density, PSA velocity, percent free PSA) and/or evaluating other serum markers (such as human glandular kallikreins and prostate specific membrane antigen). Atypical small acinar proliferation (ASAP) often represents the underdiagnosis of cancer in biopsy material; patients with cancer on the repeat biopsy usually have an elevated serum PSA. Whether the determination of serum PSA can be of help in the identification of patients with isolated prostatic intraepithelial neoplasia (PIN), i.e., long before PCa develops, is still being debated

Humans↗
PubMed2000

[Fragments of prostatic biopsy: characteristics, dimensions, and number].

Prostate needle biopsy can give important clinical information on tumor extension and grading, useful prognostic parameters for the therapeutic choice and prognostic definition. Currently about the 25% of positive biopsies for carcinoma contain only small foci of cancer that makes histopathological evaluation often the difficult and less reliable. We reviewed the literature about different methods to perform needle biopsies and methods to improve histologic yield of prostatic biopsies in order to obtain more histopathological information on the specimens to improve diagnostic accuracy on core biopsy. We report our initial experience using the preembedding methods proposed by Rogatsch. The best method to perform a prostate biopsy includes the use of using 18-gauges needles, single specimen identification and subsequent orientation of every bioptic fragment by inking its proximal end. We performed the preembedding technique of the fragments, proposed by Rogatsch et al., stretching the fragment between two nylon meshes enclosed in a tissue cassette in formalin. The full length of the biopsy is within the section plane. This technique partially modified in our preliminary experience with the employment of two sponges containing 10% buffered formalin placed in a tissue cassette (2.8 x 3.3 cm). This "sandwich" technique has furnished evident advantages for the pathologist, optimizing the visible area for section plane in comparison to that obtainable from free floating core biopsies. In conclusion, routinely application of the preembedding prostatic core biopsies could improve the accuracy of the histopathological examination and therefore provide more reliable data on tumor extension and grade.

Biopsy, Needle↗
PubMed1999

Inference network-based analyses of the histopathological effects of androgen deprivation on prostate cancer.

The evaluation of prostate cancer histology following hormonal therapy often represents a diagnostic problem for the pathologist. Previous studies have shown that an inference or Bayesian belief network (BBN) offers a descriptive classifier useful for the accurate analysis of morphological changes in individual cases of prostate neoplasia. Three different BBNs were evaluated in 94 cancer foci present in 20 radical prostatectomy (RP) specimens and in the matching biopsies in which the initial diagnosis of prostatic adenocarcinoma was made. Ten RP specimens were from patients treated with total androgen ablation or combination endocrine therapy (CET) before surgery. The first and second BBN allowed the identification with high certainty of the cancer foci present in the biopsies and RP specimens, as well as their Gleason grade, the belief value often being close to 1.0. The results of the second BBN showed a good correspondence between the Gleason grade given in the biopsies and that in the RP specimens, except in the surgical material of the treated patients, in which upgrading was always present. The third BBN showed the existence of three subgroups in treated RP specimens, one with morphological effect, another with poor effect, and the third with the histology of untreated (i.e. unaffected) cancer. In conclusion, an inference network-based analysis allows the characterization of treated prostate cancers according to the degree of histopathological change.

Adenocarcinoma↗
PubMed1999

Epithelial tumours of the adult kidney.

The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation.

Adult↗
PubMed1999

Effect of total androgen ablation on pathologic stage and resection limit status of prostate cancer. Initial results of the Italian PROSIT study.

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%, respectively). The initial results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens. These two effects are more pronounced after six months of NHT than after three months of therapy. The same degree of beneficial effects are not observed in clinical C tumours.

Adenocarcinoma↗
PubMed1999

Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma.

Villous adenoma originating in the urinary tract is uncommon. We present the first study of a large number of cases of villous adenoma of the urinary tract with clinical follow-up. Our series consisted of 15 patients with isolated villous adenoma and 8 patients with coexistent adenocarcinoma. The tumors occurred in elderly patients and had a predilection for the urachus, dome, and trigone of the urinary bladder. The typical clinical presentation was hematuria and irritative symptoms, and endoscopic examination usually identified a tumor growth. There was no gender predominance. Light microscopic examination showed morphologic similarity to colonic villous adenoma in all cases. Each tumor was composed of pointed or blunt finger-like processes lined by pseudostratified columnar epithelium. The epithelial cells displayed nuclear stratification, nuclear crowding, nuclear hyperchromasia, and occasional prominent nucleoli and mitotic figures. There was intense carcinoembryonic antigen immunoreactivity on the luminal surfaces (89%). Most cases (78%) contained cytoplasmic acid mucin, demonstrated by Alcian blue periodic acid-Schiff stain. Cytokeratin 20 was positive in all cases, cytokeratin 7 was positive in 56% of cases, and epithelial membrane antigen was positive in 22% of cases. Recurrence or invasive adenocarcinoma did not develop in any patient with isolated villous adenoma during a mean follow-up of 9.9 years. Lung metastasis developed in one patient with coexistent adenocarcinoma and multiple recurrences in another (mean follow-up, 3 years). We conclude that the prognosis is excellent in patients with isolated villous adenoma, and complete surgical resection is curative. Patients with coexistent adenocarcinoma may experience recurrence or distant metastasis, and more aggressive treatment may be indicated.

Adenocarcinoma↗
PubMed1999

Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

BACKGROUND: Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-pi expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5-alpha-reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. OBJECTIVE: To investigate GST-pi expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. MATERIALS: Immunostaining with anti-GST-pi antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. RESULTS: Diffuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-pi was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diffuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. CONCLUSIONS: Following chronic treatment with finasteride the immunohistochemical expression of pi class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GST-pi inducer.

Aged↗
PubMed1999

Subtle morphological and molecular changes in normal-looking epithelium in prostates with prostatic intraepithelial neoplasia or cancer.

BACKGROUND: Prostate cancer develops over an extended period of time. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown. METHODS: Analytical and quantitative methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) are associated with or possibly preceded by changes in the chromatin of secretory cell nuclei. The changes are detectable with a Bayesian belief network and quantifiable by computer image analysis in prostatic tissue that still appears histologically normal. In addition, normal-looking prostate epithelium shows some molecular changes similar to those present in the associated preneoplastic and neoplastic lesions. Such changes are also occasionally present in normal prostate glands without PIN and cancer. CONCLUSIONS: The subtle morphological and molecular changes of normal-looking epithelium might be seen as the onset of the development of prostatic neoplasia.

Adenocarcinoma↗
PubMed1999

Tissue architecture analysis in prostate cancer and its precursors: An innovative approach to computerized histometry.

AIMS: It is the aim of these studies to derive a numerically defined progression index for prostatic intraepithelial neoplasia (PIN) lesions. METHODS: Histometric and karyometric features were automatically extracted from images of histopathologic sections by a machine vision system. RESULTS: Both histometric and karyometric measures lend themselves to the defining of a progression index. Karyometric features were found to be more sensitive. They allow the detection of very early change. CONCLUSIONS: It is possible to measure progression of PIN lesions with precision. The methodology would lend itself for measurement of regression due to chemopreventive intervention.

Artificial Intelligence↗
PubMed1999

Role of neoadjuvant treatment in clinically confined prostate cancer. Takeda NHT Italian Group.

OBJECTIVE: This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy. METHODS: Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy. RESULTS: Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors. CONCLUSIONS: Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.

Adenocarcinoma↗
PubMed1999

Nodular hyperplasia of the prostate. Quantitative evaluation of secretory cell changes after treatment with finasteride.

OBJECTIVE: To quantitatively evaluate the changes in the secretory cells in nodular hyperplasia of the prostate after treatment with finasteride. STUDY DESIGN: Secretory cell nuclear and nucleolar measurements were performed with an image analyzer in hematoxylin-and-eosin-stained sections of 20 untreated and 20 finasteride-treated cases of nodular hyperplasia. An immunoperoxidase method was used to stain the secretory cells with a monoclonal antibody-directed, anti-prostate specific antigen (PSA). The size of prostates was determined by transrectal ultrasound. For both groups the serum PSA values were determined. RESULTS: After six months of treatment with finasteride, the prostates shrank by approximately 20% with the therapeutic regimen (as determined by transrectal ultrasound), whereas the serum PSA values decreased by 30% (before therapy, < 4.00 ng/mL). The secretory cells appeared smaller than those from the untreated group of patients, and the cytoplasm staining of the PSA marker was slightly diminished. Karyometric analyses showed that the nuclear and nucleolar size were smaller in comparison with the controls. In particular, the mean nuclear and nucleolar area in the treated group were, respectively, 34.12 and 1.424 micron 2, whereas in the untreated group the values were 40.46 and 2.261. CONCLUSION: Reduced androgen stimulation after treatment with finasteride induces involution of secretory cells. This may be responsible for the decrease in the serum PSA level and may contribute to the reduction in prostate size.

Aged↗
PubMed1999

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

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.

Adenocarcinoma↗
PubMed1999

Distinguishing cortical adrenal gland adenomas from carcinomas by their quantitative nuclear features.

OBJECTIVE: To explore data from a set of cases of adrenal cortical adenomas with different endocrine syndromes and carcinomas to determine whether quantitative image analysis of nuclear features might be used to separate the groups. STUDY DESIGN: Fifteen adrenal cortical tumors in which clinical information and optimally preserved, paraffin-embedded tissue were available were used. There were 10 adenomas and 5 carcinomas. Among the adenomas, five were associated with primary hyperaldosteronism (Conn's syndrome) and five with Cushing's syndrome. Five-micrometer-thick sections were stained with hematoxylin and eosin. In each case 50 nuclei were measured, and a number of morphometric and densitometric features were extracted. The data were subjected to multivariate analysis. RESULTS: Quantitative analysis showed that nuclei from adrenal carcinomas are larger than those from adenomas. Total optical density (OD) had a near-diploid distribution in the adenomas, while it was clearly aneuploid in the carcinomas. The pixel OD histograms were almost identical for all groups. Differences in nuclear chromatin texture were found between adenomas and carcinomas and also between the two adenoma categories. Multivariate analysis showed good discrimination between carcinomas and adenomas (Wilks lambda = .628, P < .0001) and between adenomas. However, based on Bayesian decision boundaries, 20-25% of carcinoma nuclei could be expected to be in the range of adenoma, and about 12% of Cushing's adenoma nuclei and 15% of Conn's adenoma nuclei would be classified as carcinoma. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex.

Adenoma↗
PubMed1999

Case-based prediction of survival in colorectal cancer patients.

OBJECTIVE: To develop an approach to the prediction of survival in patients with colorectal cancer using nearest neighbor analysis and case-based reasoning. STUDY DESIGN: A total of 216 patients with full clinicopathologic records and five-year follow-up were the subjects of this study. They were divided into a core database of 162 cases and a test group of 54 cases, with follow-up on all patients. When the patient was still alive at the end of the follow-up period, censored survival time was used. For each of the test cases, the four closest neighbors from the database were retrieved and their median survival time recorded and used as the predicted estimate of survival. Case matching was based on a Euclidean multivariate distance measure for the three best predictor variables: patient age, Dukes stage and tubule configuration. Cases with the smallest distance from the test case were considered to be the most similar. The predicted survival times for the test cases were compared with the actual, observed survival in the test cases to determine the success of this approach. RESULTS: The results showed reasonable concordance between observed and predicted survival figures, although there was a large degree of spread. Classification of cases into < or = 60 and > 60 months' survival showed a correct classification rate of 63%. For the prediction of survival time, the distribution of differences between observed and predicted survival times for the uncensored test cases had a median value of--5 months but also showed a wide dispersion of values. Correlation of observed and predicted survival times, while not reaching statistical significance at P < .05, did show a strong positive association. CONCLUSION: Case-based approaches to the prediction of survival times in cancer patients are important. The results of the current study illustrate the difficulties in applying this approach to survival data and highlight the complexity of patient information and the inability to accurately predict patient outcome on a small subset of clinicopathologic features. While extensive work needs to be carried out to improve prediction power, this study illustrates the potential for case-based analyses. The ability to retrieve feature-matched cases from hospital patient databases has clear, independent advantages in patient management, but the ability to provide reliable, targeted prognostic estimates on individual cases should be a common goal in medical research.

Adult↗
PubMed1999

Changes in the normal-looking epithelium in prostates with PIN or cancer.

BACKGROUND: In prostatic neoplasia, the time from tumour initiation and progression to invasive carcinoma often begins in men in the fourth and fifth decades of life and extends across decades. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown. METHODS: Quantitative and analytical methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) are associated with or possibly preceded by changes in the chromatin of secretory cell nuclei. The changes are detectable with a Bayesian belief network and quantifiable by computer image analysis in prostatic tissue that still appears histologically normal. In addition, normal looking prostate epithelium shows some molecular changes similar to those present in the associated preneoplastic and neoplastic lesions. Such changes are also occasionally present in normal prostate glands without PIN and cancer. CONCLUSIONS: The subtle morphological and molecular changes of normal looking epithelium might be seen as the onset of the development of prostatic neoplasia.

Adenocarcinoma↗