Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit “Regina Elena” National Cancer Institute

Neurological Sciences - The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and...     

Sphenoidal metastasis from prostate carcinoma. Case report and review of the literature

A case of an uncommon sphenoidal metastasis from prostate carcinoma with cranial nerve involvement is described. Current concepts of metastatic spread of this tumor to the skull base, clinical signs and therapeutic approaches are reviewed in the light of the available literature.     

Surgical anatomy of the radial nerve at the elbow

An anatomical study of the brachial portion of the radial nerve with surgical implications is proposed. Thirty specimens of arm from 20 fresh cadavers (11 male, 9 female) were used to examine the topographical relations of the radial nerve with reference to the following anatomical landmarks: acromion angle, medial and lateral epicondyles, point of division between the lateral and long heads of the triceps brachii, lateral intermuscular septum, site of division of the radial nerve into its superficial and posterior interosseous branches and entry and exit point of the posterior interosseous branch into the supinator muscle. The mean distances between the acromion angle and the medial and lateral levels of crossing the posterior aspect of the humerus were 109 (±11) and 157 (±11) mm, respectively. The mean length and calibre of the nerve in the groove were 59 (±4) and 6 (±1) mm, respectively. The division of the lateral and long heads of the triceps was found at a mean distance of 126 (±13) mm from the acromion angle. The mean distances between the lateral point of crossing the posterior aspect of the humerus and the medial and lateral epicondyles were 125 (±13) and 121 (±13) mm, respectively. The mean distance between the lateral point of crossing the posterior aspect of the humerus and the entry point in the lateral intermuscular septum (LIS) was 29 (±6) mm. The mean distances between the entry point of the nerve in the LIS and the medial and lateral epicondyles were 133 (±14) and 110 (±23) mm, respectively. Our study provides reliable and objective data of surgical anatomy of the radial nerve which should be always kept in mind by surgeons approaching to the surgery of the arm, in order to avoid iatrogenic injuries.     

Supraorbital keyhole approach for removal of midline anterior cranial fossa meningiomas: a series of 20 consecutive cases

The paper describes a retrospective study of a consecutive series of 20 midline anterior cranial fossa meningiomas (five of the olfactory groove, 14 of the tuberculum sellae, and one clinoidal), which were operated on via a supraorbital keyhole approach between 2002 and 2008. The series includes three males and 17 females (mean age 57 years, mean size of the tumors 3.5 × 3 cm, and mean follow-up 48 months). Gross total excision was achieved in 18 cases and subtotal resection in two. Out of 14 patients with visual deficits, nine patients improved, one remained stable, and three deteriorated. Two patients presented a recurrence 3 years after surgery. One peri-operative death was recorded. The subgroup of patients with tuberculum sellae meningiomas was analyzed in details. A meta-analysis of the major series of such meningiomas in the last 20 years has been performed in order to compare results of different surgical techniques. With regard to primary outcomes of these tumors, gross total removal, restoration of visual function, morbidity, mortality, and recurrence rates, the supraorbital approach, for selected cases, seems to offer valuable results, comparable with those reported in conventional and endoscopic approaches and with very low surgical aggressiveness. However, statistical data available from the literature, particularly on visual function, are still too limited to draw definitive conclusions. The best surgical option for the individual patient cannot yet be standardized and should be chosen on the basis of tumor anatomy, pre-operative clinical symptoms, and surgeon’s experience.     

Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence

The ageing process is characterized by a progressive exhaustion of the na?ve T cell reservoir that is accompanied by a compensatory expansion of effector/cytotoxic CD8+CD28- T cells. However, the origin and function of this subpopulation is not completely clarified. In this study, we examined the intracellular cytokine profile in purified CD8+ T cells obtained from 29 healthy subjects of different ages. Type 1 (IFN-gamma IL-2 and TNF-alpha) and type 2 (IL-4, IL-6 and IL-10) cytokines were determined in three CD8+ T subsets, i.e. CD95-CD28+ (na?ve), CD95+CD28- (effector/cytotoxic), and CD95+CD28+ (memory). As a general trend, we observed, in aged subjects, an increase of type 1 and type 2 intracellular cytokines within the three CD8+ subsets. In particular, we showed that type 1 cytokine-positive cells significantly increased, with age, among all the CD8+ subsets, while a marked increase of type 2 producing cells was observed only in memory CD8+ T cells. These profound changes are compatible with inflame-aging, an hypothesis which suggest that immunosenescence is mainly driven by a chronic antigenic load which not only induces an enormous expansion of CD28- T cells, but also increases their functional activity, exemplified by an high frequency of cells positive for pro-inflammatory cytokines.     

Spontaneous cerebrospinal fluid rhinorrhea as the presenting symptom of sellar pathologies: three demonstrative cases

Spontaneous rhinorrhea due to sellar pathologies is a rare and insidious disease that may represent a diagnostic challenge. Since the precipitating cause is not apparent in most patients, delayed diagnosis and/or improper treatments are not uncommon and may be detrimental for the patients. The precise mechanisms of such rhinorrhea are still incompletely understood. Proposed etiological factors include constant cerebrospinal fluid pulsations against the anterior skull base trasmitted by primitive or acquired arachnoid invaginations in combination with either elevated ICP or congenital/pathologic erosions of sellar and parasellar bone structures. Advances in the diagnosis and surgical techniques have recently modified the decision-making approach to this pathology. The present paper reports three unusual cases of sellar pathologies revealed by rhinorrhea as the first symptom discussing controversial issues on pathogenesis, complications and current management of this kind of fistula.     

Epigenetic silencing of miR-145-5p contributes to brain metastasis

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145''s promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.     

Na?ve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus

Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composition of its main subsets: naïve, central memory and effector memory T cells, in 131 cytomegalovirus (CMV) seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T cell numbers, which was mainly due to variability of the CD8 + CD28− T cell subset regardless of age. Analysis, by multiple regression, of distinct factors revealed that age was a predictor for the loss in absolute number of naïve T cells, but was not associated with changes in central or effector memory CD8+ T cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1 antigens of CMV, predicted CD28 − CD8+ T cell, antigen-experienced CD8+ T cell, and even total CD8+ T cell numbers, but not naïve CD8+ T cell loss. These results indicate a clear dichotomy between the homeostasis of naïve and antigen-experienced subsets of CD8+ T cells which are independently affected, in human later life, by age and antigen-specific responses to CMV, respectively.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-013-9594-z) contains supplementary material, which is available to authorized users.