Biomedical subjects

A Santinelli

Publications and source records attributed to A Santinelli.

At least 37 records · Page 2Linked to original sources

PubMed1999

bcl-2 expression and apoptotic bodies in 13-cis-retinoic acid (isotretinoin)-topically treated oral leukoplakia: a pilot study.

In a double-blind study 10 patients with oral leukoplakia were treated daily (three topical applications) with 0.1% isotretinoin gel or a placebo for 4 months. Nine patients completed the treatment, while one patient was lost to follow-up. Subsequently, the patients who had received the placebo used the active medication for an additional 4 months. All patients treated with the active medication showed a significant improvement of the oral lesions while, in the patients receiving only the placebo, the size of the lesions remained the same. Also the group of patients who received the active medication after the placebo showed an improvement in the size and clinical appearance of the lesions. A complete response was defined as the complete disappearance of the lesion as assessed by visual inspection, while a partial response was defined as a 50% or more reduction in the size of the lesions. In total we had a complete response and eight partial responses. No side-effects from the use of the gel were ever observed. The percentage of bcl-2-positive cells was evaluated in the basal layer from a minimum of 1000 cells in each case and the bcl-2 immunostaining was scored using three groups: - (< or = 10% cells); + (< or = 50% cells); +2 (> or = 50% cells). The presence of apoptotic bodies was evaluated in a random fashion in the parabasal layer in 20 HPF. Immunohistochemical analysis for bcl-2 protein showed that before treatment a weak positivity of the basal layers, with a focal positivity of some parabasal cells, was present: five out of nine specimens were positive. Only a few apoptotic bodies were observed. After treatment in almost all specimens it was possible to observe a complete bcl-2 negativity with a positivity in only one specimen out of nine. An increase in apoptotic bodies was observed. Statistical analysis showed that the difference between the bcl-2 positivity in the two groups was not statistically significant (P = 0.134) while, on the contrary, the difference in the count of the apoptotic bodies between the same two groups was statistically significant (P = 0.0193). In conclusion, the data obtained from this pilot study show that good results can be obtained with the topical use of 13-cis-retinoic acid.

Administration, Topical↗

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

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↗

PubMed1998

Expression of proliferating cell nuclear antigen in ameloblastomas and odontogenic cysts.

The identification of the proliferative activity in tumours may be useful to predict the biological behaviour of different lesions. Proliferating cell nuclear antigen (PCNA) has been used for the evaluation of the proliferative ability of many lesions. In this study 22 ameloblastomas (4 follicular, 5 plexiform, 4 acanthomatous, 5 unicystic, 4 recurrent), 12 odontogenic keratocysts (OKC), 8 dentigerous cysts (DC), and 12 radicular cysts (RC) were analysed. PCNA+ cells were present in all cyst types but the OKC contained the highest number of PCNA+ cells. In OKC the location of PCNA+ cells was mainly suprabasal. In ameloblastoma PCNA+ cells were located mainly in the peripheral portion of the tumour islands. Statistical analysis showed that ameloblastoma had higher PCNA+ cell counts than OKC (P < 0.0001); OKC had higher values than DC and RC (P < 0.0001). Recurrent ameloblastoma presented higher PCNA+ cell counts than other types of ameloblastoma, while unicystic ameloblastoma showed lower values than acanthomatous, plexiform and follicular ameloblastomas (in this latter case the difference was not statistically significant). These data could help to explain the different biological behaviour of these lesions.

Ameloblastoma↗

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

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↗

PubMed1996

Quantitative study of ductal breast cancer progression. A progression index (P.I.) for premalignant lesions and in situ carcinoma.

The diagnostic subjective assessment of ductal premalignant proliferative lesions and in situ carcinoma of the breast produces unsatisfactory results. Since the phenotypical cell changes in tumour progression toward infiltrating cancer constitute a continuum, a grading on a continuous scale of values produces a more reliable and reproducible characterization. The diagnostic assessment for any individual patient may be expressed by a progression index (P.I.): its numerical values are based on the cellular changes measured in the individual cases. In this study, the progression index is based on two morphometric features, nuclear size and nucleolar area. In addition, the method presented may produce a ratio, stating the relative likelihood that each case represents one of the conventional diagnostic categories. Such a likelihood ratio may be obtained from the bivariate distribution of nuclear size and nucleolar area for the conventional diagnostic categories.

Breast Neoplasms↗

PubMed1996

A flow cytometric study of early gastric cancer. The detection of high proliferative activity adds important information to the prognosis.

The prognostic value of DNA ploidy and proliferative activity has been rarely investigated in early gastric carcinoma (EGC). In the present study the ploidy pattern and cell cycle related parameters were evaluated in formalin-fixed paraffin-embedded specimens of 71 followed-up EGCs and compared with that of 20 advanced gastric carcinomas (AGC) using flow cytometry. The results showed that ploidy pattern did not affect patient outcome. On the contrary, EGC with a high S-phase had a worse prognosis. No significant differences in proliferative activity were detected between EGC and AGC. Fatal EGC had an S-phase higher than AGC. In conclusion, proliferative activity seems to affect the prognosis of EGC independent of the stage and could contribute to the identification of aggressive types of EGC.

Adult↗

PubMed1995

Long-term follow-up in early gastric cancer: evaluation of prognostic factors.

Four hundred and fourteen cases of early gastric cancer (EGC), diagnosed between 1977 and 1993, were studied. The percentage of EGC increased from 1977 to 1984, but thereafter remained more or less stable, despite a continuous increase in the number of endoscopic examinations. Three hundred and ninety-six patients were followed up. Twenty-nine patients died from the tumour, giving a 5-year survival rate of 82.8 per cent. The 'large' size type of EGC, the presence of submucosal penetration, and lymph-node metastasis showed a highly significant association with a lower survival rate. A small number of patients died despite the presence of 'favourable' prognostic factors. Other still unknown factors may therefore be important in determining the aggressive behaviour of certain EGCs.

Adult↗

PubMed1994

Centrocytic-like lymphoma associated with localized amyloidosis of the large intestine.

A case of low-grade centrocytic-like (CCL) B-cell lymphoma involving the large intestine, the regional lymph nodes and the spleen is reported. In the large intestine the lymphomatous infiltrate was restricted to sites of intense antigenic stimulation (diverticula, appendix, ileo-caecal valve) and was associated with marked plasma cell differentiation and massive amyloid deposits. The immunophenotype was CD20, CD21, CD45RA/MB1/MT2, CD68, CD45 related/Ki-B3 and HLA-DR positive, and MB2, DBA.44 reactive regarding the CCL cell lymphoma subpopulation; and IgG-lambda positive regarding its plasma cell fraction.

Aged↗

PubMed1994

Gastric dysplasia: a ten-year follow-up study.

The results of a ten-year follow-up study on gastric dysplasia (GD) are reported. A total of 260 cases were diagnosed, 125 of which had an adequate follow-up, 81 Low Grade Dysplasia (LGD) and 44 High Grade Dysplasia (HGD). Patients with LGD were younger than patients with HGD, while no significant difference in the mean age was found between HGD and carcinoma. LGD regressed in 49.4% of cases, persisted in 18.5% and progressed in 32.1%. HGD regressed in 4.6%, persisted in 13.6% and progressed in 81.8%. In some cases dysplasia reappeared after a long-time interval of apparent regression. In 58 cases progression to cancer was observed: in 35 cases dysplasia was associated with carcinoma (8 LGD and 27 HGD), while in 23 cases dysplasia evolved into carcinoma (14 LGD and 9 HGD). There was a good correlation between the accuracy in following up the patients and the chance of diagnosing the carcinoma at an early stage. The importance of gastric dysplasia as a marker for carcinoma, its precancerous nature and the treatment of the patients are discussed.

Aged↗

PubMed1994

Quantitative study of ductal breast cancer progression. Morphometric evaluation of phenotypical changes occurring in benign and preinvasive epithelial lesions.

Fifty-nine cases of Breast Epithelial Proliferative Lesions (BEPL) and Ductal Carcinoma in Situ (DCIS), were studied by image analysis, to evaluate the nuclear changes occurring in the conventional diagnostic categories of ductal hyperplasia, atypical ductal hyperplasia and DCIS with quantitative methods. Diagnosis reproducibility is the main practical problem of these breast lesions. In fact, with subjective methods, the reproducibility appears to be very low and precarious especially for clinical demands. The objective, quantitative evaluation of cell phenotypical changes should be the method for both practical diagnostic problems and study of ductal cancer progression. The distribution pattern of the data in the feature, obtained with quantitative analysis, strongly suggests a continuum of changes, indicating an evolutionary process of Breast Ductal Carcinoma (BDC) progression in its preinvasive stage. Each observed case may be characterised by its own cellular, objective alterations and a progressive trend toward BDC can be stated. Since the actual changes of the proliferative phenotypes can be measured, and the values are reproducible, karyometric measurement may allow an objective grading of individual cases.

Adult↗

PubMed1993

Dose dependent effects of protracted ingestion of small amounts of gliadin in coeliac disease children: a clinical and jejunal morphometric study.

This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.

Celiac Disease↗

PubMed1993

Computed cell cycle and DNA histogram analyses in image cytometry in breast cancer.

AIMS: To analyse the cell cycle and DNA histogram components in data from DNA static cytometry and, in particular, to investigate the influence of the length of time the slides are exposed to the light of the cytophotometer in evaluating the G0/G1 peak. METHODS: DNA static cytometry was performed on 18 Feulgen stained imprints and six histological sections taken from six breast carcinomas. The total optical density values obtained were analysed using software commercially available as Multicycle. DNA flow cytometry was performed on the same cases. RESULTS: The proportions of nuclei related to the cell cycle components from DNA static cytometric data, obtained from Feulgen stained cytological smears, were almost identical with those obtained from DNA flow cytometric data. Moreover, additional information was obtained from the DNA static cytometry frequency histogram and the proportions of nuclei below the diploid G0/G1 peak and above the G2 phase. Discrepancies between DNA static cytometry and DNA flow cytometry were seen in the large coefficients of variation of the G0/G1 peaks obtained with the former method of analysis, even though a better correspondence was found when the exposure time of the slides to the light of the cytophometer was conspicuously shortened. The information obtained from histological sections seemed to be similar to that obtained from DNA flow cytometry when a single cell population was present; a single cell population was detected in two out of the three cases in which two distinct populations had been present in DNA flow cytometry. CONCLUSIONS: The computer analysis of DNA static cytometric data obtained from Feulgen stained cytological specimens provides the type of information on the cell cycle which is usually obtainable only from DNA flow cytometry. Correspondence with the DNA data from histological sections, however, was poor.

Breast Neoplasms↗

PubMed1992

Evolutionary somatic cell changes in cervical tumour progression quantitatively evaluated with morphological, histochemical and kinetic parameters.

The somatic cell changes which characterise malignancy evolution in human cervical preneoplastic and neoplastic lesions have been assessed on histological sections by means of a computerised image analyser. Many features have been simultaneously measured on each cell of the lesions studied, and the following results have been obtained: Some features, mainly kinetic, show continuously increasing values which express changes correlated to the increasing malignancy; other features, especially related to nuclear atypia, cellular heterogeneity and the degree of aneuploidy, have values dropping at the level of early stromal infiltration, which can be morphometrically characterised as composed of relatively homogeneous phenotypes; these features seem to express the degree of genetic instability and relate to the evolutionary somatic cell changes; tumour progression evolves through sequential discontinuous steps, each of them characterised by specific phenotypical features of the neoplastic cell population; the neoplastic cells in the foci of early stromal infiltration and vascular invasion, phenotypically more homogeneous than the parent cell populations of carcinoma in situ and infiltrating carcinoma, seem to possess a greater genetic stability.

Aneuploidy↗

PubMed1992

Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features.

The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate.

Adenoma↗

PubMed1992

Epithelial dysplasia of the gastric mucosa. A morphometric and ploidy pattern study.

60 cases of gastric dysplasia (20 mild, 20 moderate and 20 severe) were quantitatively studied and compared with cases of hyperplastic polyp (No 10), intestinal metaplasia (No 20), peptic ulcer (No 10) and invasive adenocarcinoma (No 20). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured in Feulgen stained tissue sections by means of a Leitz TAS. The stepwise discriminant analysis demonstrates that severe dysplasia and adenocarcinoma can be well distinguished from mild and moderate dysplasia. The ploidy pattern study demonstrates that the presence of severe dysplastic changes corresponds to a sharp increase in the degree of aneuploidy. In peptic ulcer, intermediate values between "benign" and "malignant" lesions were found.

Adenocarcinoma↗

PubMed1992

Quantitative study of the precancerous and malignant lesions in colorectal adenomas.

150 endoscopically removed colorectal adenomas are quantitatively studied. In 90 cases dysplastic glands constituted the entire lesion (30 mild, 30 moderate, 30 severe); in 60 cases foci of adenocarcinoma were present (30 intramucosal, 30 submucosal). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured from Feulgen-stained paraffin sections. The results show a continuous neoplastic progression in the trends of the morphometric parameters as well as in the ploidy pattern. The stepwise discriminant analysis defined the morphometric features of the atypical nuclei, which were present in small numbers also in mild dysplasia; they progressively increased in number, reaching the maximum in submucosal carcinoma.

Adenocarcinoma↗