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Biomedical subjects

D Di Stefano

Publications and source records attributed to D Di Stefano.

At least 19 recordsLinked to original sources
PubMed2006

Computed tomography in suspected local breast cancer recurrence.

PURPOSE: The purpose of this prospective study was to test computed tomography (CT) in the evaluation of local breast cancer recurrence. MATERIALS AND METHODS: Our study population included 103 women referred for mamma CT examination for reasons of suspicious findings in a conservatively treated breast. In these patients, both clinical and conventional imaging studies (mammography, ultrasonography) features of local recurrences were non specific or suspicious. The patients underwent breast CT before and 90 s after intra-venous contrast medium administration. Criterion for cancer recurrence was detection of a lesion with an enhancement of 20 UH or more. The final diagnosis was based on operative histopathological findings or follow-up for over two years. RESULTS: Local recurrence was confirmed on histology in 52 patients. CT identified 47 breast recurrent cancers. False-positive contrast enhancement was seen in five patients. CT showed 90% sensitivity, 90% specificity and 90% accuracy. CONCLUSION: Although mamma CT examination proved to have a high diagnostic efficacy in evaluating breast cancer recurrence, routine computed tomography is unnecessary for most patients.

Adult↗
PubMed2006

A case of intraroot cauda equina cavernous angioma: clinical considerations.

STUDY DESIGN: Case report and literature review. OBJECTIVE: Intradural-extramedullary cavernoma is a rare condition with only 23 cases reported in the literature. Most cases described adhere to spinal root or spinal cord. We report an example of this rare entity located within the sheets of one cauda equina nerve root. SETTING: Rome, Italy. METHODS: The authors report clinical, radiological, surgical, and pathological features of intraroot cavernoma with a literature review. RESULTS: Patient was operated. One year after surgery, he was healthy. CONCLUSION: Lumbar intradural cavernous angioma may present with sciatalgia, low-back pain, neurological deficit, or, more rarely with subarachnoid hemorrhage or hydrocephalus. They are treated successfully with surgical resection but preoperative status is a predicting factor for outcome. Sometimes the sacrifice of the spinal root is inevitable because, as in present case, the cavernous angioma is included in the nerve root. These lesions are rare and benign lesions. It is important for neurosurgeons to be aware of the existence of this entity to avoid preoperative misdiagnosis with tumor.

Aged↗
PubMed2006

Post-radiation intramedullary malignant peripheral nerve sheath tumor.

We report the intramedullary growth of a malignant peripheral nerve sheath tumour (MPNST). A 50year-old man developed a severe tetraparesis over a 4-month period. Following irradiation of a chronic tonsillitis during his childhood, the patient had later experienced a number of post-radiation diseases, including a laryngeal cancer that required permanent tracheotomy. Before admission, a magnetic resonance imaging (MRI) study had disclosed a C4-C5 intramedullary lesion. On admission to our Department, the patient had a nearly complete tetraparesis. At surgery, the lesion was exposed through a posterior midline myelotomy. A friable neoplasm, with no clear plane of cleavage, was found. The tumour was subtotally resected. Histological examination, which intraoperatively had not yielded a specific diagnosis, eventually revealed a MPNST, grade intermediate, with ultrastructural and immunohistochemical features consistent with a schwannian differentiation. No postoperative radiotherapy was undertaken. The patient died 9 months later from pneumonial complications. MPNSTs may develop within the spinal cord similarly to their benign schwannian counterpart. The reported sequence of events might support a possible relation between irradiation of the spinal cord and induction, followed by malignant transformation, of intramedullary schwannosis. This unique case must be added to the growing list of radiation-induced spinal cord tumours.

Cell Movement↗
PubMed2004

Cranklike conformational transitions in polyethylene.

Molecular dynamics simulations of a variety of polymeric systems provide the evidence for two different kinds of conformational transitions: independent single bond transitions and cranklike transitions (or correlated bond transitions). While single bond transitions can be rationalized according to standard theories of activated processes controlled by the saddle point crossing, a more complex description is required for the other type of transitions. In a recent work devoted to the analysis of the simplified chain model with three rotors [B. Nigro and G. J. Moro, J. Phys. Chem. B 106, 7365 (2002)], a theory has been proposed for cranklike transitions represented as a kinetic process between equilibrium states differing by two torsional angles (i.e., two bond transitions). Moreover their rate coefficients were estimated on the basis of a local expansion about the bifurcation of the separatrices departing from the potential function maximum. In the present work the same theory is applied to a model for long alkyl chains in solution, in order to rationalize the behavior of cranklike transitions in polyethylene and to recognize the molecular features controlling them. We obtain probabilities of occurrence of cranklike transitions in substantial agreement with simulation results. Furthermore, the theory is capable of explaining the dependence of the rate on the separation between the two reactive bonds, as well as the dependence on the conformational state of the starting configuration. In particular, selection rules for next-to-nearest neighbor transitions are recovered from the shape of the separatrices and the location of the corresponding bifurcations.

Journal Article↗
PubMed2003

Human pituitary tumours express the bHLH transcription factors NeuroD1 and ASH1.

Among the transcription factors involved in pituitary ontogenesis and physiology, basic helix-loop-helix (bHLH) have been poorly studied. Members of bHLH family include NeuroD1 and ASH1, both involved in neuroendocrine differentiation. We evaluated their mRNA expression patterns, by semi-quantitative RT-PCR analysis (sq-RT-PCR) and/or Northern blot, in a series of 33 pituitary adenomas (PA), anterior pituitaries, and pituitary cell lines. Immunohistochemistry for NeuroD1 was also performed in 25 PA. Low levels of NeuroD1 were observed in normal pituitaries and in the somatomammotroph cell lines GH3/GH4C1, contrasting with high levels in corticotroph AtT20 cells. NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11). According to sq-RT-PCR analysis, overexpression of NeuroD1 compared to normal pituitaries was frequent. Variable nuclear NeuroD1 immunopositivity was also present in about 70% of studied cases. ASH1 mRNA was widely detected in normal pituitaries, in all tumour cell lines and in most PA (84%), with measurable levels in corticotroph (5/5) and CNS (9/11) adenomas, and in a significant subset of PA derived from Pit-1 dependent lineages (9/16). We conclude that: a) NeuroD1 is differentially expressed in PA and its possible ontogenetic and/or pathogenetic implications in non-corticotroph PA are discussed; b) ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells.

Adult↗
PubMed2002

A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

Adenoma↗
PubMed2001

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy.

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.

Adolescent↗
PubMed2001

Two familial giant pituitary adenomas associated with overweight: clinical, morphological and genetic features.

OBJECTIVE: Pituitary adenomas are usually sporadic, although rare familial cases have been described. Here we report two first degree female cousins with giant pituitary adenoma and overweight. Both presented with secondary amenorrhoea, occasional headache and weight gain. MATERIALS AND METHODS: In both patients clinical, morphological and genetic studies were performed. Both patients underwent surgery and post-operative medical therapy with somatostatin analogues and dopamine agonist, followed by a conventional radiotherapy course. RESULTS: Clinical examination at presentation revealed an acromegaloid habitus only in the second patient. Basal and dynamic hormonal evaluation showed high serum GH and serum IGF-I values, higher in the second than in the first patient, and a mild hyperprolactinaemia only in the first patient. On optical and electron microscopy, both tumours were oncocytic adenomas, immunopositive for GH in the first patient and GH/prolactin in the second. The genetic analysis for germ-line mutations of the multiple endocrine neoplasia type 1 gene was negative. Two years after radiotherapy a remarkable shrinkage of both tumours was observed, whereas the overweight worsened in both patients, accompanied by high plasma leptin values. CONCLUSION: To our knowledge, this is the first report of familial pituitary adenomas including one case of a clinically silent GH-secreting adenoma. In addition, it provides further evidence that familial pituitary tumours can occur as a multiple endocrine neoplasia type 1 unrelated disease.

Adenoma↗
PubMed2000

Radiation injury involving the internal carotid artery. Report of two cases.

Radiation therapy is an uncommon cause of stenosis and occlusions of the cervical internal carotid artery (ICA). We describe two cases of cerebral ischemia due to ICA stenosis in patients irradiated for malignant tumors (lymphoma and breast cancer). The first patient, a 32-year-old man, presented with an episode of cerebral ischemia. Six years previously he had received irradiation therapy for a left laterocervical mass histologically diagnosed at biopsy as a Hodgkin's lymphoma. Cerebral angiography on entry revealed bilateral occlusion of the cervical ICA, with a 2-cm stump at the origin of the left ICA. Despite anti-platelet aggregation therapy the ischemic attacks persisted, necessitating a stumpectomy. After vascular-repair surgery the patient had no further ischemic symptoms. The second patient, a 42-year-old woman, began to experience the sudden onset of pain in the right arm and left hemiparesis five years after surgery plus irradiation (4500 rad) for breast cancer, and three years after excision of a single cerebral metastasis. Cerebral angiography obtained on admission showed occlusion of the right ICA and right subclavian arteries, both lesions necessitating thrombectomy. After surgery the right radial pulse immediately re-appeared and the hemiparesis regressed. In both patients, 2-year follow-up assessment by Doppler ultrasonography and magnetic resonance angiography (MRA) confirmed that the operated arteries remained patent. These two unusual cases underline the potential risk of irradiation-induced ischemic cerebrovascular symptoms, suggesting that patients who have received radiation therapy to the neck and mediastinum who survive for more than 5 years should undergo regular non-invasive imaging of neck vessels (Doppler ultrasonography and MRA).

Adult↗
PubMed1999

Pleomorphic xanthoastrocytoma with CT and MRI appearance of meningioma.

We describe a pleomorphic xanthoastrocytoma (PXA) in a young girls whose frontal lobe location, solid structure, dural tail and MRI signal characteristics led to a preoperative diagnosis of meningioma. PXA should be considered in differential diagnosis of tumours affecting young patients with neuroradiological characteristics suggestive of meningioma.

Adolescent↗
PubMed1999

p16 (INK4a, MTS-1) gene polymorphism and methylation status in human pituitary tumours.

OBJECTIVE: The p16 gene, which encodes a physiological inhibitor of the cyclin D-CDK4 complex, is now considered as an important tumour-suppressor gene in a variety of tumours. A marked reduction of its expression has been reported to occur without significant genetic alterations in human pituitary adenomas, although rare point mutations of uncertain functional significance have been described. On the other hand, p16 gene silencing due to hypermethylation has been reported in several human primary tumours. The aim of this study was to further investigate the pathogenetic events leading to p16 gene inactivation in pituitary tumours. DESIGN: To screen a european series of human pituitary tumours for p16 gene alterations and possible gene hypermethylation. PATIENTS: A representative series of 31 human pituitary tumours-30 macroadenomas, including a MEN-1 non-secreting pituitary adenoma and a non-MEN-1 familial giant GH-secreting adenoma, and one FSH-secreting pituitary carcinoma-was studied. METHODS: Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for p16 gene alterations in all cases. Direct sequencing of PCR-products was obtained by the di-deoxynucleotide method where suspected abnormalities of the PCR-SSCP analysis were observed. In 24 samples, a methylation-specific PCR assay (MSP-PCR) was used to determine p16 gene methylation status. RESULTS: Two sporadic cases of pituitary adenomas had a similar single A to G base substitution leading to an heterozygous Ala140Thr p16 polymorphism, which has not previously been described in such tumours, but is known to be functionally silent. No other p16 abnormality could be suspected from PCR-SSCP analysis in this series. In contrast, the presence of methylated-specific PCR products was observed in 20/24 cases (83.3%). CONCLUSIONS: This study confirms that p16 gene mutations are not involved in the pathogenesis of human pituitary tumours, although polymorphisms can be demonstrated, depending on the population considered. In contrast, the high incidence of hypermethylation of the p16 gene suggests that such an alteration occurs early in pituitary tumours, and may play a role in pituitary tumorigenesis.

Adenoma↗
PubMed1998

Uterine diffuse adenomatoid tumor. Does it represent a different biological entity?

Adenomatoid tumor represents a type of mesothelioma apparently confined to the genital tract and characterized by its benign behavior. Its morphological aspects are well known and, until now, it has been described as a nodular mass except for a case diffusely infiltrating the entire myometrium in an immunosuppressed patient. We report a case of benign mesothelial tumor characterized by histological, immunophenotypical and ultrastructural features of an otherwise typical adenomatoid tumor but diffusely growing below uterine serosal surface into the myometrium without discernible borders. The existence of a diffuse type of adenomatoid tumor might reflect a different nature of this neoplasm leading to the hypothesis that this variant of benign mesothelioma represents a distinct biological entity.

Adenomatoid Tumor↗
PubMed1998

Epidermal growth factor binding sites in human pituitary macroadenomas.

The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with Kd1 = 0.62 +/- 0.23 nM and Kd2 = 53.8 +/- 8.2 nM for the high- and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10.2 fmol/mg membrane protein, range 0.0-332.0). EGF-receptor positivity, defined as EGF binding > or = 10.0 fmol/mg protein, was observed in 23 samples (54.8%), especially in prolactinomas (76.5%, P < 0.05 vs other tumors taken together) and in gonadotrope adenomas (62.5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12.8 vs 0.0 fmol/mg membrane protein, P = 0.047), and especially in adenomas invading the sphenoid sinus (median 26.7 fmol/mg membrane protein, P = 0.008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P = 0.15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.

Adenoma↗
PubMed1997

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

Adult↗
PubMed1996

Relationship between thallium-201 uptake by supratentorial glioblastomas and their morphological characteristics on magnetic resonance imaging.

Single-photon emission tomography (SPET) with thallium-201 is used in the assessment of patients with gliomas because the amount of 201Tl accumulated by the tumoral cells increases in proportion to the degree of tumour malignancy, thus making it possible to differentiate high-grade from low-grade gliomas or recurrences from radiation necrosis. However, in large areas of tissue such as those examined in 201Tl SPET studies, the uptake of 201Tl may vary considerably even in tumours with the same histological diagnosis, as occurs in glioblastomas (GBMs). In order to evaluate the possible influence of the macroscopic characteristics of tumours on 201Tl uptake, we studied a series of 13 patients with histologically proven GBMs, comparing magnetic resonance imaging (MRI) parameters such as tumour dimensions, perilesional oedema, intratumoral necrosis and contrast enhancement with the degree of 201Tl uptake. The patients underwent both 201Tl SPET and MRI before surgery. The 201Tl index (tumour/contralateral unaffected brain) was calculated using two different region of interest (ROI) methods: the first employed irregular large ROIs (3.2+/-13.9 cm2) including pixels with more than 50% maximum activity; the second employed regular square small ROIs (2.7 cm2) centered on the maximum activity of the lesion. Of the MRI morphological parameters studied, only necrosis significantly reduced the degree of 201Tl uptake in GBMs when larger ROIs were used. However, by using small regular ROIs the influence of necrosis on 201Tl uptake was found to be less relevant. Since necrosis is related to tumour proliferative activity and represents a negative prognostic factor in astrocytoma, a possible underestimation of 201Tl uptake due to intratumoral necrosis must be carefully evaluated.

Brain↗