Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

The efficacy and tolerability of cyclosporine G in human kidney transplant recipients.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.     

Primary gastric non-Hodgkin's lymphoma in a population-based registry.

BACKGROUND. The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. METHODS AND RESULTS. We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the province of Varese, Northern Italy. From 1978 to 1987 we identified 3261 cases of gastric neoplasms, 119 of which were gastric NHL: 32 (1.87%) from 1978 to 1982, and 87 (5.32%) from 1983 to 1987. The difference in the age and sex standardized incidence trend between these two time periods was statistically significant (p < 0.001). The overall survival rate of the 112 evaluable patients was 54% at 5 years and 45% at 10 years. A multivariate analysis was performed. Age (p < 0.0005), clinical stage (p < 0.04) and therapy (p < 0.0005) were found to be significant prognostic factors for survival. CONCLUSIONS. This study stresses the utility of prospective randomized clinical trials that could indicate the optimal management of patients with primary gastric lymphoma.     

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.