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Biomedical subjects

G Serio

Publications and source records attributed to G Serio.

At least 19 recordsLinked to original sources

Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.

Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.

Adult↗

[The stereotaxic core breast biopsy using the Mammotome: an alternative to intraoperative examination].

The aim of this work was to evaluate the accuracy of vacuum-assisted biopsy by comparing it with frozen biopsy. 141 stereotaxic biopsies were performed by Mammotome (Ethicon Endo-Surgery, Hamburg) from January 2000 to March 2001. Biopsies were performed for microcalcifications (n = 105, 74.5%), irregular opacities (n = 20, 14.2%), regular opacities (n = 6, 4.2%), stellate lesions (n = 10, 7.1%). Histological analysis showed 85 (60.3%) benign lesions, 46 (32.6%) malignant lesions including (21 cases of carcinoma in situ and 25 invasive carcinomas) and 10 (7.1%) atypical lesions. All malignant lesions were subjected to surgery. In three cases (1 in situ and 2 invasive), core biopsy was excisional and no residual lesion was observed. Two of the carcinomas in situ revealed invasive features on the surgical biopsy. One of the atypical lesions was underestimated and the final diagnosis was "well differentiated carcinoma in situ." Only three of benign lesions underwent surgery after Mammotome biopsy. Among the 55 frozen-section biopsies of mammographically detected breast lesions performed in the same period, were one false-positive and 3 false-negative cases, while in 4 cases the diagnosis was deferred after paraffin embedding. Our results confirmed Mammotome biopsy as an effective alternative and a more reliable method than frozen-section examination.

Biopsy, Needle↗

[The Ljubljana classification of epithelial hyperplastic laryngeal lesions: a morphometric evaluation of nuclear pleomorphism].

Epithelial hyperplastic laryngeal lesions (EHLL) are associated, with a varying degree of "epithelial risk"- to develop invasive carcinoma. Several classifications have been proposed but none has received a total agreement. The 1999 Ljubljana classification distinguished four grades: simple, abnormal and atypical hyperplasia and in situ carcinoma (ISC). The first two grades are considered benign lesions; the ISC is the malignant lesion, while the atypical hyperplasia is considered a "risky lesion". This is characterized by alterations of epithelial cells towards malignancy, but not to the extent to be found in carcinoma cells. Such characteristics refer to cytomorphological (e.g., nuclear hyperchromatism, nucleoli, increased nuclear/cytoplasmic ratio) and architectural (e.g. stratification, orientation, maturation) features. In the Ljubljana scheme, nuclear pleomorphism is one of the most important features. We wanted to improve the importance of nuclear pleomorphism in the basal cells layer in different classes of EHLL using morphometrical analysis. We studied 8 cases of simple hyperplasia, 10 of abnormal hyperplasia, 10 of atypical hyperplasia and 8 of ISC using the software SAM (Shape Analytical Morphometry). The results were submitted to univariate statistical analysis. Nuclear dimensions (maximum diameter, perimeter and area) showed a progressive increase from simple to atypical hyperplasias to ISC, while abnormal hyperplasia showed the lowest values. On the contrary, analytical parameters related to nuclear contour irregularities and asymmetries showed their highest values in abnormal hyperplasia nuclei. There were no significant differences between atypical hyperplasia and ISC, while it was possible to differentiate abnormal hyperplasia from the others. In conclusion basal nuclei of atypical hyperplasia and ISC are similar so that other cytological and morphological architectural parameters are necessary to distinguish the two lesions. Abnormal hyperplasia seems to be the biological category of 'proliferative " benign laryngeal epithelium; simple hyperplasia refers to "stable" - irritative epithelium.

Biopsy↗

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

AIMS: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival. METHODS AND RESULTS: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively). CONCLUSIONS: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

Adult↗

Quantitative morphometrical investigation of basal cell layer in laryngeal premalignant lesions.

Histological diagnosis of laryngeal dysplasia is quite subjective. Since morphometry is highly reproducible, this method was applied to compare shape and size variations of the basal nuclei of the laryngeal epithelium in normal, laryngeal intraepithelium neoplasia (LIN) and invasive carcinoma to assess the reliability of light microscopic criteria used in grading dysplasia according to Friedman classification. Morphometrical analysis was carried out by Shape Analytical Morphometry (S.A.M) system. The logical architecture assumes that each irregular shape contains elements of two distinct logical domains: gross distortions that interest the contour and its local perturbations. These features were investigated separately by analytical procedures to acquire independent parameters both on the logical level and the numerical one. The nuclear area significantly increased from normal to carcinoma (p<.001). The increasing of the nuclear area was evident also in LIN I. Nuclear distortions were present in LIN II and LIN III. The highest nuclear contour irregularities were found in LIN III. Multivariate analysis showed a difficulty in discriminating various grades of dysplasia, especially between LIN I and LIN II (31% of error). In conclusion, our results indicate that nuclear pleomorphism of the basal cells layer, using a unique evaluator, is an unsatisfying criterion to distinguish moderate dysplasia.

Analysis of Variance↗

Sex chromosome loss, micronuclei, sister chromatid exchange and aging: a study including 16 centenarians.

In the present study we analysed the possible effect of age, sex and smoking on the mean values of micronucleus (MN) and sister chromatid exchange (SCE) frequencies on peripheral blood obtained from 38 subjects ranging in age from 16 to 63 years and 16 centenarians. The mean number of binucleated cells with micronuclei varied in function of age and sex (as demonstrated by the analysis of covariance (F=13.13; P<0.001), particularly evident was the increment observed in women with increasing age (interaction age/sex: F=5.53; P<0.05). Smoking habits had no effects on MN frequency (F=0.36; P>0.05). Sex (F=4.18; P<0.05) and smoking habits (F=14.64; P<0.001) influenced significantly SCE per cell frequencies, but age had no effects on them (F=2.45; P>0.05). The age-associated increase of sex chromosome loss was studied using fluorescence in situ hybridisation (FISH) on interphase nuclei. The loss of Y signals was observed in approximately 10% of interphase cells from the centenarians males, that is six times more often than in the younger control men (approximately 1.6%). The frequency of X signal loss (approximately 1.7%) in young women was similar to that observed in male controls of the same age but the incidence of the X chromosome aneuploidy in centenarian females was appreciably higher (approximately 22%) than that found for the Y chromosome in males. These results were correlated with the data on MN formation and a positive correlation between the percentage of aneuploid cells (FISH) and MN values was observed (r=0.50; P<0.05).

Adolescent↗

Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa.

BACKGROUND: Gain-of-function mutations of the c-kit protooncogene, mainly clustered in the juxtamembrane domain, have been reported in a significant fraction of gastrointestinal (GI) stromal tumors (GISTs) that represent the most common mesenchymal tumor of the GI tract. Two families also have been described with a GIST predisposition syndrome with a germline c-kit mutation affecting either the juxtamembrane domain or the tyrosine kinase domain. Here, the authors report on a family in which the dominantly inherited trait of hyperpigmented spots was inherited from an individual who developed multiple GISTs with diffuse hyperplasia of the myenteric plexus by his son, who was affected with urticaria pigmentosa. METHODS: Screening for the c-kit mutation was performed by means of polymerase chain reaction-based denaturing gradient gel electrophoresis/constant denaturing gel electrophoresis followed by direct sequencing of abnormal conformers. Expression of KIT and CD34 was determined by immunohistochemistry. RESULTS: In peripheral blood DNA samples, both affected family members showed a previously undescribed c-kit mutation in the juxtamembrane domain, resulting in the substitution of alanine for valine(559). Mutation and polymorphic marker analyses on DNA samples from three GISTs and two skin biopsy specimens evidenced the same mutation in the heterozygous condition. Immunohistochemical examination showed coexpression of CD117 (c-kit) and CD34 in all independent GISTs and CD117 positivity in mast cells from the skin lesions. CONCLUSIONS: Comparative analysis of clinical presentation and mutation mapping in the families described to date point to the peculiar association of mast cells, melanocytic dysfunction, and GIST predisposition in carriers of c-kit mutations within the juxtamembrane domain.

DNA Mutational Analysis↗

Predictability of monthly and yearly rhythms of breast cancer features.

In order to evaluate if breast cancer biological characteristics undergo significant menstrual and seasonal variations, we analysed in a consecutive series of 905 breast cancer patients, steroid receptor level (ER and PgR by DCC assay), proliferative activity (3H-Thymidine Labeling Index, 3H-TLI) and size of primary tumour in relation to calendar date and day of menstrual cycle at the time of the surgical procedure. For data analysis, the method of time series construction and classical spectral analyses with Bartlett Kolmogorov-Smirnov test for white noise (BKS test) was utilised. For what concerns menstrual variations, 3H-TLI showed a significant periodicity (t = 0.3146, p < 0.01 by BKS test) with peaks at day 12nd and day 18th; ER showed a significant periodicity (t = 0.3605, p < 0.01 by BKS test) with more evident peak at day 27th; PgR, a significant periodicity (t = 0.160, p = 0.05 by BKS test) with peaks at day 15th and day 24th, similar to that observed for tumour size (t = 0.19, p < 0.05 by BKS test). With respect to yearly fluctuations, 3H-TLI showed only a trend for a significant rhythm (t = 0.16, p = 0.06 by BKS test) with peaks in May and November; ER a significant periodicity (t = 0.2099, p < 0.05 by BKS test) with two evident peaks in January and April; also for PgR a significant periodicity (t = 0.3161, p < 0.05 by BKS test) was demonstrated with a peak in July; finally, tumour size showed a significant rhythm (t = 0.335, p < 0.01) paralleling 3H-TLI behaviour. Finally, the analysis of variance with interaction of menstrual and seasonal timings showed that only the seasonal timing was able to independently influence the 3H-TLI variations (3H-TLI higher in spring). We confirmed that breast biology has significant menstrual and seasonal variations and that the seasonality is probably the timing factor more relevant in periodicity determination.

Breast Neoplasms↗

Fine needle aspiration cytology of primary lymphoma of the thyroid: a report of 17 cases.

Between 1980 and 1998, 4272 thyroid surgical specimens with a preoperative fine needle aspirate were sent to our Anatomical Pathology Department. Among these cases there were 17 primary thyroid lymphomas, which constituted 0.3% of all the thyroid lesions and 2.3% of the thyroid malignancies. Seven cases were diffuse large B-cell (DLBC) lymphomas and 10 were MALT lymphomas. Of the DLBC lymphomas six were correctly diagnosed by fine needle aspiration cytology (FNAC) and one was diagnosed as positive for malignancy, and among MALT lymphomas four were diagnosed as lymphoma, four as suspicious for lymphoma, and three as Hashimoto's thyroiditis (HT). Our data indicate that the diagnosis of primary thyroid lymphoma of high grade is easy, and immunocytochemistry (ICC) can confirm suspicious cases. The diagnosis of MALT lymphoma is more difficult; ICC can confirm suspicious cases, and false-negative results seem to be caused by sampling error, because HT usually coexists with MALT lymphoma.

Adult↗

The clivus-supraocciput angle: a useful measurement to evaluate the shape and size of the fetal posterior fossa and to diagnose Chiari II malformation.

OBJECTIVE: To obtain a nomogram of the clivus-supraocciput angle as a basis for the diagnosis of Chiari II malformation in fetuses with ventriculomegaly. METHODS: A cross-sectional study was undertaken on 310 normal pregnant women of 16-34 weeks' gestation. A mid-sagittal section of the fetal skull was obtained and the angle between the clivus and the supraocciput was measured. Forty-four fetuses with ventriculomegaly due to various causes (13 Chiari II malformation, 12 dysgenesis of the corpus callosum, 7 aqueductal stenosis, 6 borderline ventriculomegaly, 3 Dandy-Walker malformation, 2 porencephaly, 1 schizencephaly) were also included in the study and the values of the angle found in the pathological cases were compared with those found in the normal population. RESULTS: The clivus-supraocciput angle did not change during gestation and was almost constant with an average value of 79.3 +/- 6 degrees. All cases of Chiari II malformation showed a value below the 5th centile of our nomogram. CONCLUSIONS: The evaluation of the posterior fossa and particularly the measurement of the clivus-supraocciput angle is a useful parameter to differentiate the various causes of fetal ventriculomegaly and particularly to recognize Chiari II malformation.

Adolescent↗

Response of severe HIV-associated thrombocytopenia to highly active antiretroviral therapy including protease inhibitors.

OBJECTIVE: To investigate the response of HIV-associated severe thrombocytopenia (STP) to highly active antiretroviral therapy (HAART) including protease-inhibitors. METHODS: In this retrospective study, 15 patients with HIV-associated STP (platelet count < 50 x 10(9)/l mostly antiretroviral experienced (13/15), underwent HAART for at least 6 months (median 21; range 6-41 months) during which the platelet (PLT) count and plasmatic HIV-RNA were monitored. The PLT response was compared to that observed in 19 patients previously treated with zidovudine (AZT) monotherapy. RESULTS: HAART induced a significant increase in the PLT count (chi(2)=10.53, P=0.01) within the third month which was sustained up to the sixth month of therapy. No STP relapse was observed among eight PLT responders followed for longer than 6 months (median 27; range 7-41 months). The PLT increase after HAART was similar to that observed with AZT monotherapy, but a greater number of HAART patients were antiretroviral-experienced. HAART determined a PLT response in 10/13 subjects whose thrombocytopenia had not improved after previous AZT monotherapy. After 6 months of HAART, a complete platelet response occurred more frequently in patients with undetectable plasma HIV-RNA levels (P=0.01). CONCLUSIONS: HAART induces a sustained PLT response in HIV-associated STP, even in antiretroviral-experienced subjects and in those with AZT-resistant thrombocytopenia. An undetectable plasma HIV viraemia induced by HAART is necessary for STP recovery.

Adolescent↗

[Polycystic mesothelioma of the peritoneum. Description of 4 cases].

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.

Abdominal Pain↗

Initial experience with sentinel lymph node mapping and biopsy in breast cancer. Preliminary results on 80 consecutive patients.

Sentinel node biopsy, in breast cancer, is a promising surgical technique for predicting histological findings in the remaining axillary lymph nodes, especially in patients with clinically node-negative breast cancer. 80 patients with breast cancer were evaluated for enrollment in this study. For mapping procedure 32 patients underwent lymphoscintigraphy in combination with an injection of vital blue dye, while 48 utilized only vital dye. In all patients, after sentinel node (SLN) biopsy, a complete axillary dissection was performed. The mapping procedure was possible in 79 cases (98.7%). The SLNs were positive in 27 (34.1%), in 52 patients SLNs were negative and in 50 of these all axillary nodes were negative. There was concordance in 77/79 cases (97.4%). The false negative rate was 3.8% (2/52). The overall sensitivity of the SNL biopsy was 93.1% (27/29), with a negative predictive value of 96.1% (50/52). This study demonstrates that accurate SLN identification was obtained combining lymphoscintigraphy and blue dye. Moreover, each method requires a suitable learning curve. Further studies are needed to define an accurate patient selection and the most speedy and precise method for intraoperative histological examination of SLNs.

Adult↗

Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors.

OBJECTIVES: To evaluate the presence of premature atherosclerotic lesions of epiaortic vessels in HIV-1-infected protease inhibitor-(PI) treated patients compared with PI-naive patients and healthy individuals. DESIGN: One-hundred and two HIV-1-positive patients, including 55 treated with PI for at least 12 months and 47 either naive or treated with PI-sparing regimens, were subjected to epiaortic vessel ultrasonography. These data were compared with those obtained from 104 healthy individuals. METHODS: Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the chi-square test, Mantel-Haenszel test, odds ratio and logistic regression analysis. RESULTS: Of the PI-treated patients, 29 out of 55 (52.7%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in seven out of 47 (14.9%) PI-naive patients. Of the 104 healthy individuals, seven cases (6.7%) of intimal medial thickness were noted. A slightly significant correlation was found between carotid lesions and age, male sex and hypercholesterolaemia, whereas cigarette smoking, hypertriglyceridaemia and Centers for Disease Control and Prevention stage significantly increased the risk of vascular lesions (P= 0.022, P= 0.017 and P= 0.079 respectively). However, the highest significance regarded use of PI (P= 0.011). These results were confirmed by logistic regression analysis. CONCLUSIONS: These data demonstrate a higher than expected prevalence of premature carotid lesions in the PI-treated compared with PI-naive patients. If confirmed, a periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.

Adult↗

Unusual prostatic adenocarcinoma with endocrine basophilic FSH-immunoreactive cells.

We report an unusual variant of prostatic adenocarcinoma with marked endocrine differentiation (mixed endocrine-exocrine adenocarcinoma). Endocrine cells accounted for 60% of the tumour cells, were positive with silver impregnation and for chromogranin A, synaptophysin, and neuron-specific enolase, and coexpressed the exocrine antigens prostatic acid phosphatase and prostatic-specific antigen. Most of the endocrine cells were basophilic with haematoxylin-eosin and proved immunoreactive for alpha subunit of human chorionic gonadotropin and follicle-stimulating hormone. The remaining endocrine cells were represented by eosinophilic cells positive for serotonin, and by calcitonin and serotonin-immunoreactive cells not identifiable in haematoxylin-eosin-stained sections. On ultrastructural analysis, two types of endocrine cells were identified. The most frequent cell type showed abundant cytoplasmic round, electron-dense neurosecretory granules, either small (212+/-44 nm) or large (471+/-114 nm), resembling those of gonadotropic pituitary cells. The second type of endocrine cells contained irregular electron-dense granules similar to those of serotonin-storing enterochromaffin cells.

Adenocarcinoma↗

Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1.

To better understand whether potent antiretroviral therapies can modify the natural history of HIV-1-associated microsporidiosis and cryptosporidiosis, the response to antimicrobial treatment of these opportunistic infections was evaluated in patients with or without antiretroviral treatment. Fifty patients with diarrhoea, all positive for Cryptosporidium parvum or Enterocytozoon bieneusi, were included in the study. Retrospective data were collected concerning demographics, clinical and microbiological characteristics of the parasitic infection, antiretroviral therapy and prophylaxis against opportunistic infections. Faecal samples were prepared using the Richie formalin-ethyl acetate method and stained using the modified Ziehl-Neelsen method for detection of Cryptosporidium parvum and Isospora belli, the modified trichrome and calcofluor white technique for detection of Enterocytozoon spp., and iodine for detection of ova, cysts or vegetative forms. Diarrhoea was defined as an abnormal increase in stool liquidity, an abnormal increase in stool frequency and a daily stool weight of more than 250 g for a period of at least 4 days. Patients treated with double antiretroviral therapy or protease inhibitors demonstrated an excellent response and a sustained therapeutic effect after follow-up (range, 5-36 months). The relapse of cryptosporidiosis in two patients who discontinued antiretroviral therapy suggests that the infection might remain in a latent stage. The resolution of the diarrhoea seems to be related to an increased CD4+ cell count rather than to the viral load. In conclusion, these data strongly support the hypothesis that combination antiretroviral therapy is able to greatly modify the course of cryptosporidiosis and microsporidiosis in patients infected with HIV-1.

AIDS-Related Opportunistic Infections↗

Increased risk of lymphoproliferative disorders in relatives of patients with B-cell chronic lymphocytic leukemia: relevance of the degree of familial linkage.

We assessed the familial aggregation of chronic lymphoproliferative diseases (CLD) in 3962 relatives of 169 patients with B-cell chronic lymphocytic leukemia (B-CLL). Data collection included a self-administered questionnaire. The "relative risk" considered the connection between a higher incidence of CLD and the degree of familial linkage with the probands. The model of logistic regression was statistically significant (p < 0.001), with the probability of CLD increasing in proportion to the relationship coefficient between parents, siblings and children [(relationship coefficient 0.5; probability of CLD 1.85 (C.I. 95%, range 1.1-3%)]. CLD, particularly B-CLL, were observed in first-degree relatives of the patients with B-CLL more often than in other relatives.

Adult↗