Giampaolo Cantore

Long-term follow-up of intramedullary spinal cord tumors : A series of 202 cases

OBJECTIVE:To review a series of patients who underwent surgical removal of intramedullary spinal cord tumors, focusing on the long-term functional outcome, recurrence rates for the various tumors, and technical problems continually debated in neurosurgical practice. METHODS:From December 1972 to June 2003, 202 patients underwent removal of intramedullary tumors. Lesions were located in the cervical spinal cord in 61 patients (30%), at a dorsal site in 60 (29%), at a cervicodorsal site in 51 (25%), and in the medullary cone in 30 (15%). The most frequent histological tumor types were astrocytomas (86 patients, 42%) and ependymomas (68 patients, 34%). RESULTS:Of the 68 ependymomas, 55 (81%) were completely removed and 13 (19%) incompletely removed. In 66% of the patients (42 patients), the presenting signs and symptoms remained unchanged at long-term follow-up; in 25% (16 patients), they improved; and in 9% (6 patients), the clinical status worsened. Of the 27 Grade I astrocytomas, 22 (81%) were completely removed and 5 (19%) incompletely removed. Functional assessment of the 23 patients available at “late” follow-up showed that 26% (6 of 23 patients) had improved, 9% (2 of 23 patients) had worsened, and 66% (15 of 23 patients) remained unchanged from preoperative status. Conversely, of the 41 Grade II astrocytomas, only 5 (12%) were completely removed, and 10% had improved. None of the 18 Grade III to IV astrocytomas could be completely removed. In 61% (11 of 18 patients), the postoperative functional status worsened. CONCLUSION:Determinant predictors of a good outcome after surgery for intramedullary spinal cord tumors are histological type of lesion, complete removal of the lesion, and a satisfactory neurological status before surgery.

Cerebral oligodendroglioma: prognostic factors and life history.

The records of 137 patients with supratentorial oligodendroglioma treated surgically between 1953 and 1986 were reviewed. The tumors were rated histologically benign or malignant. In the 105 patients followed up with a minimum observation time of 5 years to December 1991, the mean postoperative survival was 90.2 months (standard error, 9), the median 64 months (standard error, 9.6), the 5-year survival rate 52.4%, and the 10-year survival rate 24%. Sixteen possible prognostic factors, broken down into two or more variables each, were considered in the survival study on univariate methods (5-year survival rate, survival curves, and Coxs hazard function) and on multivariate analysis according to Coxs stepwise proportional hazards model. The latter showed that variables correlated positively with survival were benign histological findings (P, 0.000), postoperative radiation therapy (P, 0.004), and time of operation from 1977 to 1986 (P, 0.044) in 105 patients of the whole series, and period of surgery from 1977 to 1986 (P, 0.000), subtotal or total surgical resection of the tumor (P, 0.001), and radiation therapy (P, 0.005) in the subgroup of 79 patients operated on for benign tumors. However, the most interesting point to emerge from the study was the relevance of admission clinical status to the survival of patients who did not receive radiation therapy and to the prognostic response of those who did. Of the 40 patients with seizures and negative neurological status--Clinical Syndrome A--the 10 who did not receive radiation therapy had survived as long as the 30 who did (5-year survival rate, 80 versus 67%; P, not significant; median survival, 122 versus 85 months; Breslow and Mantel-Cox P, not significant), whereas of the 65 patients with intracranial hypertension and/or neurological deficits--Clinical Syndrome non-A--the 18 who did not receive radiation therapy had short survival times, and the 47 who did fared significantly better (5-year survival rate, 11 versus 53%; P, 0.002; median survival, 32 versus 64 months; Breslow and Mantel-Cox P, 0.000). These findings were not significantly affected by the exclusion of malignant neoplasms and in the group of benign tumors, in which the histological characteristics have not been found to be significantly different between those with A and those with non-A clinical syndrome, did not depend on different frequencies of subtotal or total tumor removal.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Prognostic factors in intramedullary astrocytomas

This report presents a retrospective prognostic study of 65 patients with intramedullary astrocytoma surgically treated between 1953 and 1990. Median survival and statistical survival at 5 years were assessed in relation to clinical, histological and therapeutic factors for each patient. Results showed that factors positively influencing the prognosis are low histological grade of the tumour and good pre- and post-operative general conditions. Among the grade II astrocytomas, the fibrillary and protoplasmatic types presented longer survival times regardless of the type of removal performed. In anaplastic astrocytomas the simultaneous presence of certain morphological features indicative of higher malignancy negatively influenced survival. The degree of resection did not influence average survival within each histological grade.

Ictal heart rate increase precedes EEG discharge in drug-resistant mesial temporal lobe seizures

OBJECTIVE Heart rate (HR) changes, mainly tachycardia, are often observed during seizures originating from the temporal lobe. The aim of this study was to analyze the role of ictal HR changes in localizing both mesial and lateral temporal lobe epilepsy (TLE) in a group of 68 patients. The influence of the gender and the side of epilepsy on HR modulation was also evaluated. METHODS Ictal HR was recorded during prolonged Video-EEG monitoring performed in 68 patients affected by drug-resistant TLE during a non-invasive pre-surgical protocol. According to the electro-clinical correlation, obtained by video-EEG monitoring, one hundred-thirteen seizures (n=113) and one hundred-forty-four auras (n=144) were identified and included in the study. Furthermore, the electro-clinical correlation allowed the classification of all the epileptic events (seizures and auras) as having mesial or lateral origin, based on the temporal lobe seizure onset zone. Ictal HR was calculated with respect to the R-R waves, and assessed from 15 sec (s) before (T(- 15)) to 15 s after (T(+15)) the time of EEG seizure onset (T(0)). RESULTS We observed a high incidence (92%) of ictal HR increase in TLE seizures. When the ictal EEG indicated a seizure onset from the mesial temporal structures, the onset of ictal HR increase preceded by about 5 s the EEG ictal onset (SD+/-18.4), whereas the onset of HR increase coincided with the onset of EEG discharges (SD+/-14.8) when the ictal EEG indicated the onset of seizures from the lateral temporal structures. No significant differences were found between male and female patients; and between right and left TLE. CONCLUSIONS Our findings show that ictal HR increase, preceding the onset of the EEG discharge, is associated with ictal EEG seizure pattern defining temporal lobe seizures originating from the mesial temporal lobe structures; this association suggests that the HR changes may be coupled to the functional impairment of neural circuits involved in sympathetic cardiovascular regulation, in the mesial temporal lobe structures. Further studies investigating the relationship between intracranial EEG monitoring and ECG recording are worthwhile, to confirm our results and to give further indications on the pathogenesis of ictal HR abnormalities.

Intramedullary astrocytomas and ependymonas in the pediatric age group: a retrospective study

A series of 45 pediatric patients underwent surgery for intramedullary astrocytoma or ependymoma at the Cook County Hospital or the Childrens Memorial Hospital of Chicago (Northwestern University) and the Neurosurgical Department of Rome “La Sapienza” University. Results showed that intramedullary astrocytomas and ependymomas in children differ from one another in terms of prognosis, and particularly as regards surgical strategy as an element of therapeutic management. Gross total removal of 70% of the ependymonas was achieved, in comparison to 33% of the astrocytomas. In astrocytomas the extent of resection did not significantly influence prognosis. Neurological condition on admission, regardless of oncotype, was found to be extremely influential: patients operated in good condition tended to remain neurologically stable or improve in the long term, while those operated on while in poor condition did not show any improvement at all. No definitive conclusions were possible regarding the value of radiotherapy, because it was only performed in 6 of the 45 cases. The authors limited its use to highly malignant lesions in view of the well-known sensitivity of the spinal cord to radiation, especially in children.

CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity

The activation of ion channels is crucial during cell movement, including glioblastoma cell invasion in the brain parenchyma. In this context, we describe for the first time the contribution of intermediate conductance Ca(2+)-activated K (IK(Ca)) channel activity in the chemotactic response of human glioblastoma cell lines, primary cultures, and freshly dissociated tissues to CXC chemokine ligand 12 (CXCL12), a chemokine whose expression in glioblastoma has been correlated with its invasive capacity. We show that blockade of the IK(Ca) channel with its specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) or IK(Ca) channel silencing by short hairpin RNA (shRNA) completely abolished CXCL12-induced cell migration. We further demonstrate that this is not a general mechanism in glioblastoma cell migration since epidermal growth factor (EGF), which also activates IK(Ca) channels in the glioblastoma-derived cell line GL15, stimulate cell chemotaxis even if the IK(Ca) channels have been blocked or silenced. Furthermore, we demonstrate that both CXCL12 and EGF induce Ca(2+) mobilization and IK(Ca) channel activation but only CXCL12 induces a long-term upregulation of the IK(Ca) channel activity. Furthermore, the Ca(2+)-chelating agent BAPTA-AM abolished the CXCL12-induced, but not the EGF-induced, glioblastoma cell chemotaxis. In addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 pathway is only partially implicated in the modulation of CXCL12-induced glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway is not involved. In contrast, EGF-induced glioblastoma migration requires both ERK1/2 and PI3K activity. All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents.

Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients

OBJECTIVE Transsphenoidal surgery results in biochemical remission of acromegaly in 45–80% of patients; however, few studies have addressed the impact of transsphenoidal surgery on cardiovascular function in acromegalic patients. The aim of this prospective study was to investigate the effects of postoperative GH/IGF‐I normalization on echocardiographic parameters and blood pressure (BP) in a series of patients with active acromegaly.

Supratentorial Ependymomas of the First Two Decades of Life. Long-Term Follow-up of 20 Cases (Including Two Subependymomas)

In order to better elucidate the lesser known aspects of the biological behavior and prognosis of supratentorial ependymomas in children and young adults, we studied a series of 20 patients, ages 1 to 20 years. The tumor site was extraventricular in 14 cases and intraventricular in 6 (including one third ventricle tumor). Histologically, according to World Health Organization criteria, there were 12 ependymomas (E), 2 subependymomas (SE), and 6 malignant ependymomas (ME). Of the 18 patients surviving surgery, 12 (66.6%) are alive and disease free 63 to 252 months (mean, 146 mo) after the operation; 9 harbored an E, 2 had an SE and 1 had an ME. Four patients are now out of risk of recurrence according to Collins law. Six of the long-term survivors (50%), four E and two SE, did not receive postoperative radiotherapy. However, two patients with E, initially treated by surgery alone, had a recurrence and one subsequently died. Two ME patients showed signs of spinal metastases after subsequent operation for recurrence and shortly before death. Considering the partially good results as well as failures after surgery alone in our and in other series and the risks of irradiating the childs brain, we tried to elucidate in what cases radiotherapy could be reasonably withheld, or alternatively, when prophylactic craniospinal irradiation should be prescribed. The main conclusions of our study are the following: 1) Radical surgery alone is a reasonable option as the initial treatment for lateral ventricle tumors and for solid extraventricular tumors located far from eloquent brain areas, provided the histology is benign, especially if of the SE type.(ABSTRACT TRUNCATED AT 250 WORDS)