Brain metastases in patients with advanced breast cancer.

BACKGROUND: The incidence of brain metastases (BM) is apparently rising in patients with advanced breast cancer (ABC). We performed a case control study to define current features of breast cancer related to central nervous system (CNS) metastases. PATIENTS AND METHODS: From March 1999 to May 2006, we identified 72 patients with symptomatic BM of breast cancer. A comparison group was randomly selected assigning to each case two patients with primary breast cancer and no BM, matched for year of diagnosis, age and tumour stage (pT status and nodal status). RESULTS: Cases had a significantly higher rate of negative estrogen receptors (ERs) (60% in cases vs. 29% in controls), negative progesterone receptors (PgRs) (79% vs. 43%), HER2/neu over expression (44% vs. 13%) and immunostaining for Ki-67 > or =20% (84% vs. 55%), with p-value <0.001 for all four parameters in univariate analyses. On multivariate analysis, HER2/neu over expression and Ki-67 -20% were independent predictive factors of brain relapse (Odds Ratio (OR) 2.55, 95% confidence intervals (CI) 1.10-5.94 and OR 2.97, 95% CI 1.01-8.73, respectively). Endocrine unresponsive tumours (both ER and PgR <10%) showed an increased risk of relapse with BM of borderline significance (OR 1.91, 95% CI 0.87-4.12). CONCLUSION: Patients with ER and PgR negative tumours either with or without HER-2/neu over expression should be considered at higher risk of BM.

Leucocyte rheological properties are altered in patients with diffuse atherosclerosis.

To evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs 295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25 +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35 +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC of LFA-1 on neutrophils was significantly different (p < 0.05) between group A and B patients. The percentage of aggregated leucocytes was significantly higher (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/- 0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected between groups B and C. Leucocyte number and expression of CD44 were not significantly different among the 3 groups. In conclusion, changes in leucocyte rheology are present in patients with atherosclerosis and may contribute to chronic ischaemia.

Mild brain ischemia increases cerebral lipid peroxidation and activates leukocytes in the peripheral blood of rats.

This study evaluated local and systemic leukocyte changes, respectively in the jugular and femoral veins, after an acute reduction of cerebral blood flow (oligoemia) in rats submitted either to permanent bilateral carotid occlusion (BCO) (no. = 36) for 5 hours or to sham operation (no. = 33). In a subgroup of rats (no. = 13) the extent of neural damage was histologically assessed. As a marker of biochemical brain changes the entity of the iron-ascorbate induced lipid peroxidation of synaptosomes was assessed in vitro by measuring malondialdehyde (MDA) reactive products. Five hours after surgery, the percentage of aggregated leukocytes and of activated neutrophils reducing the NBT were significantly higher in BCO rats (p < 0.05). However, leukocyte changes did not differ significantly between the jugular and the femoral districts. The brains of BCO rats showed tiny foci of neuronal necrosis. Synaptosomes obtained from the BCO animals showed a small but highly significant increase of MDA production (p < 0.01). Long-lasting brain oligoemia increases the production of lipid peroxidative metabolites, and causes the occurrence of tiny foci of neuronal necrosis in different brain regions. The lack of a significant gradient in aggregated leukocytes and activated neutrophils between the jugular and femoral venous districts demonstrates that leukocytes are stimulated in the peripheral blood by even mild biochemical and morphological brain damage.

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.

Gemcitabine-induced systemic capillary leak syndrome.

Systemic capillary leak syndrome (SCLS) is a rare disorder with a high mortality rate, characterized by rapidly developing edema, weight gain and hypotension, hemoconcentration and hypoproteinemia. This syndrome is caused by sudden, reversible capillary hyperpermeability with a rapid extravasation of plasma from the intravascular to the interstitial space. Even though SCLS has been suggested to be the pathogenic mechanism for the pulmonary toxicity of gemcitabine (GCB), a new deoxycytidine analogue with structural similarities to cytosine arabinoside, a direct correlation between GCB and SCLS has never been reported. We describe a case of repeated SCLS after GCB administration in a 51-year-old male with locally-advanced non-small-cell lung cancer treated with a combination of cisplatin and GCB. The detection of GCB-induced SCLS supports the hypothesis that SCLS could be the pathogenic way of GCB pulmonary toxicity. This finding can help to better understand and treat the potentially deadly GCB-related acute respiratory distress syndrome that is being recognized.

[Dosimetry problems of radiotherapy with electron fields of small dimension or partially shielded]. / Problemi dosimetrici nella radioterapia con campi di elettroni di dimensioni piccole o parzialmente schermati.

In radiotherapy in many clinical cases it is necessary to employ electron beams of small dimensions and/or shielded in order to have shaped fields. It is well known that percentage depth dose and output depend on the energy, on the field dimensions and on the collimation system. In order to evaluate separately the influence of these factors measurements were performed with electron beams of nominal energy from 6 to 14 MeV, of a linear accelerator Philips SL/75. Measurements were performed in standard dimension phantoms and in a small perspex phantom, 3 cm diameter. The values obtained in this small phantom were compared with the ones obtained for the same diameter collimator in order to have information on effect of missing lateral scatter equilibrium. Other measurements for an applicator, open and partially shielded, were performed. The results of these measurements are shown in graphics. Data show that the percentage depth dose ionization curves at fixed energy depend on the collimator linear dimension in particular, when these dimensions are smaller than the range of secondary electrons. However it is evident the difficulty to find a correlation between linear field dimensions and the percentage depth ionization curves. In the clinical practice it is important to take into account this difficulty when employing small or irregular electron fields.

[Nutritional status of CAPD patients in Lazio]. / Stato nutrizionale dei pazienti in CAPD nel Lazio.

Uremic patients have been shown to be frequently malnourished. The amount of glucose absorbed from dialysis solution makes caloric malnutrition unusual among CAPD (Continuous Ambulatory Peritoneal Dialysis) patients. Protein malnutrition is more likely because of loss of nutrients into the dialysate and inhibition of appetite. Present study evaluates nutritional status of 29 patients (20 F, 9 M), 60.31 +/- 16.04, on CAPD since 15.2 months (4-50). Dialysis was scored adequate in all patients, based on the Clinical Assessment Score proposed by the Columbia University Group. Nutritional status was evaluated with (1) Marckmann score, based on relative body weight (RBW), triceps skin fold (TSF), midarm muscular circumference (MAMC), S-transferrin, and (2) Subjective Global Assessment (SGA) based on history, physical examination, anthropometric (BW, skin folds, % body fat according to Durnin, MAMC) and laboratory data (S-albumin, C3, S-transferrin, Hb, lymphocyte count, creatinine appearance rate [CAR], urea nitrogen appearance normalized by BW [NUNA], protein catabolic rate [pcr]). RBW was 118.2% because of excess stored fat; % body fat was > 40% in 6 females and 34.4 +/- 5 in 14 females. Lymphocytes, total proteins, S-albumin, S-transferrin, C3, IgG were normal. CAR (12.2 +/- 3.2 mg/kg/die) and NUNA (101.1 +/- 37.3 mg/kg/die) were lower than normal, as reported for dialysis patients. Marckmann score (26 patients) defined 10 cases of slight malnutrition; SGA (29 patients) identified 2 severely and 14 slightly malnourished patients. Marckmann and SGA scoring however agreed only in 13 over 26 patients. Slight or severe malnutrition has been assessed in CAPD patients in spite of clinically adequate dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukocyte count and aggregation during the evolution of cerebral ischemic injury.

We evaluated leukocyte aggregation by means of the leukergy test and count in 26 patients with atherothrombotic stroke and in 10 patients with transient ischemic attacks. The evaluation was performed within 24 h from the onset of symptoms and then repeated on day 2, 4, 6 and 8. Data were compared with those of 10 healthy controls. Stroke patients were followed until day 30 when a clinical examination and brain computed tomography were performed to evaluate the extent and outcome of cerebral damage. Both leukocyte aggregation and count were significantly increased in stroke patients with respect to controls. While leukocyte count was not able to differentiate the severity of neurological impairment in stroke patients, leukocyte aggregation was significantly higher in major than in minor stroke patients on days 2 and 4 (p < 0.05). Moreover, while values of leukocyte count recorded at entry remained substantially stable in the following determinations in all groups, leukocyte aggregation showed a significant increase (p < 0.05) on day 4 with respect to all the other determinations in major stroke patients. These findings show that the extent and temporal profile of changes in leukocyte count and aggregation are different in patients with cerebrovascular disease and suggest an involvement of altered leukocyte rheology in the development of cerebral ischemic injury.

Infection with Helicobacter pylori and leukocyte response in patients with myocardial infarction.

To test whether Helicobacter pylori may contribute to the inflammatory response following myocardial infarction, the levels of IgG antibodies to Helicobacter pylori and some parameters of leukocyte activity were measured in 63 patients and 61 comparable controls. Helicobacter pylori-positive patients showed a significantly higher expression of the adhesion molecule LFA-1 on neutrophils than Helicobacter pylori-negative patients (433+/-29.0 vs. 398.8+/-38.9 mean fluorescence channels; P<0.0001), whereas no significant difference for any parameters tested was found in control subjects. These data suggest a role of Helicobacter pylori in inducing a leukocyte response following myocardial infarction.