The prognostic role of vessel productive changes and vessel density in oligodendroglioma.

The recognition of the anaplastic variant of oligodendroglioma is difficult, since it is not easy to identify histological prognostic factors. Among the latter, vascular productive changes have been inconsistently put in relation with survival. In 95 cases of operated oligodendrogliomas, endothelial cell hyperplasia, microvascular proliferations and capillary density were studied by histological and immunohistochemical methods. Capillary density was evaluated on CD31-stained sections by a grid of 100 squares placed in the ocular of the microscope. Statistical analysis was performed in order to compare these parameters with survival. A nodular growth pattern was observed more frequently among tumor grades 3-4 than among tumor grades 1-2. Endothelial cell hyperplasia was more frequent in nodular growth pattern, but it did not correlate with survival. The highest capillary density was found in nodular growth pattern, but it did not correlate with survival as well. Microvascular proliferations correlated with survival only in univariate, but not in multivariate analysis. Age, extent of surgical removal, year of surgery, post-operative Karnofsky score and MIB-1 LI remained associated with survival, as observed in a previous study.

[Vascular access in hemodialysis. Surveillance and role of percutaneous transluminal angioplasty]. / Accessi vascolari in emodialisi. Sorveglianza e ruolo dell'angioplastica percutanea transluminale.

The function of vascular shunts in hemodialysis plays a vital role for the efficiency and effectiveness of replacement therapy. A study was performed in 147 patients undergoing periodical hemodialysis with distal FAV (no = 86), proximal FAV (no = 33), PTFE grafts (no = 23), Canaud-Tesio catheters (no = 7). A protocol for function evaluation was developed which also included the calculation of overall recirculation (R), that was found to be 10.8 + 7% (using the three blood sample method). In 28/143 patients the monitoring protocol recommended the use of angiography which identified abnormalities in 78% of cases, before the onset of thrombotic phenomena. In particular, surgical radiology was able to resolve 94% of cases in which angiography revealed a stenosis using percutaneous transluminal angioplasty and/or the insertion of one or more stents.

Cyclin D1 expression in gliomas.

Cyclin D1 (cycD1) expression was defined immunohistochemically using monoclonal antibody DCS-6 and polyclonal antiserum H-295 in 50 glioma biopsies. The number of positive nuclei was higher for H-295 than for DCS-6, with a ratio of 3:1. The labelling index (LI) was compared to the grade of histological malignancy and to Ki-67 MIB-1 LI. The LI for cycD1 increased with histological malignancy, in parallel with the increase in MIB-1 LI. In most tumours, the maximum LI for cycD1 and MIB-1 were found in the same areas. The mean MIB-1 LI: mean cycD1 LI ratio does not vary in the three grades of astrocytic tumours. However, in this study the correlation between the two LIs was not statistically significant. Staining for cycD1 antigen does not necessarily imply that the gene is overexpressed since other molecular mechanisms can also be responsible for cell cycle deregulation. In invasive areas, the cycD1 LI is frequently higher than in solid tumour, either because more tumour cells are positive or because reactive astrocytes and activated microglia express cycD1. The relative contribution of neoplastic and reactive cells remains to be defined.

CDKN2/p16 inactivation and p16 immunohistochemistry in astrocytic gliomas.

CDKN2/p16 inactivation is the most frequent alteration in the molecular regulation of G1-S transition. CDKN2/p16 homozygous deletions was studied in paraffin-embedded sections of 45 astrocytic tumours by multiplex PCR. Immunohistochemistry for p16 and proliferation marker Ki-67 MIB-1 was performed in adjacent sections; their labelling index (LI) have been calculated. CDKN2/p16 gene was not deleted in astrocytomas, while homozygous deletion was found in 26.7% anaplastic astrocytomas, and in 55.0% of glioblastomas. Analysis of CDKN2/p16 homozygous deletion in discrete areas of the same tumour, showed that the deletion occurred independently of the phenotypic aspect of the areas. Nevertheless a genotypic and phenotypic heterogeneity is present in few cases. p16 immunohistochemistry mostly corresponds to the genotypic pattern. No correlation was found between CDKN2/p16 homozygous deletion and MIB-1 LI.

Prognostic factors in oligodendroglioma.

BACKGROUND: A reliable marker for tumor oligodendroglial cells is not yet available, so that the histological recognition of the tumor still encounters uncertainties. There is no general agreement also on prognostic factors in oligodendroglioma. The inconsistency concerns mainly the histopathological factors. The aim of the study was recognition of prognostic factors in oligodendroglioma. METHODS: In a series of ninety-eight oligodendrogliomas, including twenty mixed oligoastrocytomas, clinical [sex, age at surgery, tumor location, symptoms at presentation], therapeutic [extent of resection, year of surgery, post-operative Karnofsky score, post-operative radiotherapy, post-operative chemotherapy], histological [cell density, nuclear pleomorphism, vascular endothelial proliferation, necrosis, microcysts, mitoses, mitotic index (MI), apoptosis, apoptotic index (AI)] and immunohistochemical parameters [MIB-1 and PCNA Labeling Indexes (LIs), staining for GFAP, positivity for p53] were correlated with survival in uni- and multivariate analysis in order to identify their prognostic significance. RESULTS: Age at surgery, extent of surgical resection, year of surgery, post-operative Karnofsky score and MIB-1 LI were associated with survival in both uni- and multivariate analysis. Location, symptoms at presentation, mitoses, MI, AI, and PCNA LI showed a significant correlation with survival in uni- but not in multivariate analysis. The twenty cases of oligoastrocytomas did not show any difference in survival from pure oligodendrogliomas. CONCLUSIONS: Some clinical and therapeutic factors together with MIB-1 LI play a prognostic role. MIB-1 LI is prognostic with a cutoff of 8%. Histology gives a limited contribution to the prognosis. Oligoastrocytomas had the same outcome and prognostic factors as pure oligodendrogliomas.

Is medulloblastoma the same tumor in children and adults?

The appearance of medulloblastoma in adult age and the uncertain overlapping of prognostic factors in pediatric and adult populations stimulate the question of whether medulloblastoma is different in adults and in children. The pathologic features, proliferation potential and glial/neuronal differentiation have been investigated in 42 adult medulloblastomas and 42 medulloblastomas of children; the quantitative data have been compared between the two groups of age. Homer-Wright rosettes, nuclear polymorphism and histologic signs of neuronal differentiation were more frequent in children cases; GFAP-positive tumor cells and desmoplastic type were more frequent in adult cases. The mean, median and rage of Lis, with PCNA and MIB-1 were significantly (p < 0.05) higher in adults than in children. All cases, independently from age of the patients were immunoreactive with markers of neuronal commitment (class III beta tubulin isotype, MAP-2, neurofilaments). The immunoreactivity pattern suggested a more mature neuronal character in desmoplastic cases of adults than of children and in classic cases of children than of adults. In conclusion, some phenotypic differences between childhood and adult medulloblastoma exist, but do not support a substantially different course of the disease. The higher proliferation potential in adult than in childhood cases is unexpected in a tumor of embryonal origin, and reduces the applicability of Collin's law to medulloblastoma.

Role of apoptosis in the prognosis of oligodendrogliomas.

Prognostic factors in oligodendrogliomas are not well defined, even considering the labeling index of proliferation markers. As in other neuroepithelial tumors, the difficulty in calculating cell loss may contribute to this uncertainty. Proliferation markers Ki-67/MIB.1 and PCNA, mitoses, apoptotic nuclei, p53 and bcl-2 expression were investigated in 98 oligodendrogliomas. Apoptosis was assessed by the aspect of nuclei, by in situ end-labeling (ISEL) technique and by c-Jun immunohistochemical demonstration. The Bcl-2 also was immunohistochemically studied for its anti-apoptotic role. Mitotic index (MI), labeling index (LI) for MIB.1 and PCNA and apoptotic index (AI) were calculated and compared among themselves and with histology and survival. It was found that AI correlated with MI (p = 0.001) and was significantly higher in anaplastic than in classic oligodendrogliomas (p = 0.001). Apoptosis occurred only slightly more frequently in cases with high LIs for proliferation markers (MIB.1 and PCNA) (p = non-significant) and it was definitely higher in p53-positive cases (p = 0.008). It did not correlate with bcl-2 which was poorly expressed in oligodendrogliomas, with the exception of cells with astrocytic features. Apoptotic index correlated very weakly with survival (p = 0.05); therefore, it cannot be considered a highly reliable prognostic factor in oligodendrogliomas.

Cell proliferation and invasion in malignant gliomas.

Cell proliferation and invasion were studied in sixty biopsies of malignant gliomas selected to reproduce the spreading modalities identified in ninety autopsy cases of glioblastoma. Cell proliferation was studied by the immunohistochemical demonstration of PCNA and MIB-1 and by the calculation of their labeling indexes (LI). The main finding was that cell proliferation and cell invasion are not necessarily associated. The interface between the solid tumor and the adjacent brain was represented either by a gradient of tumor cell density or by a clearcut demarcation of the tumor. In the first case the LI either did not change in the infiltration area in comparison with solid tumor or it was much lower, whereas in the second case there was a ring with a high density of labeled nuclei at the tumor periphery. Perineuronal satellites were usually positive for proliferation markers. Cells accumulated in the outer cortical layers, from a deeply located tumor, were almost negative, whereas those originating from subarachnoidal or subpial invasion showed a high LI. High LIs were also found in subarachnoidal and subpial growths, and in a cell population descending into the brain parenchyma around meningeal penetrating vessels. The relationship between cell proliferation and invasion from in vivo studies is not a direct and a simple one.

Echotomography in arteriovenous fistulae.

We employed Echotomography (by 2.25-5MHz probes) as a quick procedure to measure the vessel diameter at definite points to detect aneurysms and their evolution, to evaluate the arteriovenous fistula (AVF) characteristics, to detect haematoma, thrombi, and collateral vessels. Echotomography is a non-invasive technique which may be performed repetitively even immediately after AVF surgery. It was most valuable in the examination of proximal AVF and internal shunts (autologous venous and bovine carotid grafts). Echotomography has proved to be accurate in studying the initial morphological and functional evaluation and follow-up of AVF.

["Clinical clearance" and "weekly clearance" of urea in periodical hemodialytic treatment]. / "Clearance clinica" e "clearance settimanale" dell'urea nel trattamento emodialitico periodico.

Starting from the hypothesis that small molecules are freely diffusible, a simple formula is proposed for the determination of real ureic clearance during dialysis. This automatically allows for all variables (blood flow and flow of the dialysing solution, temperature, physical and/or chemical state of the membrane, level of solute concentration, transmembrane pressure, etc.). On the basis of this formula, a calculation system is also proposed for assessing weekly ureic clearance levels and hence the real efficiency of treatment. This system may also be applied to peritoneal dialysis and permits optimisation of substitutive treatment. It is thus easier to select the best filter and rhythms for each patient.

[Kinetics of anticoagulation in hemodialysis. Sequential study of single, intermittent and continuous heparinization]. / Cinetica dell'anticoagulazione in emodialisi. Studio sequenziale sull'eparinizzazione unica, intermittente e continua.

A sequential real-time study was run to monitor plasma heparin values following three standard dose protocols during 4-hr dialysis, using an enzymatic method. One group of patients was given a single dose of 7000 IU at the commencement of dialysis, a second group 5000 IU at the start and 2500 IU at the end of the third hour, and a third group 2500 IU at the start and 1500 UI/hr for four hours. Plasma levels were checked every hour and ranged from 0.702 IU/ml (+/- 0.069) (start) to 0.290 IU/ml (+/- 0.079) (end) in the first group, 0.552 (+/- 0.116) to 0.312 (+/- 0.09) in the second, and 0.456 (+/- 0.113) to 0.314 (+/- 0.063) in the third. Correlation of heparin levels with coagulation time led to the establishment of an optimal range of 0.2 to 0.6 IU/ml.