G. Tomei

Long-term results of treatment for craniopharyngioma in children.

Abstract Results of the treatment of 27 children with craniopharyngioma are reported. A subfrontal pterional approach was used in 55.6% of cases, a transsphenoidal and a transcallosal or transcortical approach in 25.9% and 18.5% of cases, respectively. Radical removal was the goal of surgery and was achieved in 70.8% of cases treated as primary surgery. The operative mortality was 3.7% and was due to hypothalamic failure. Most (81.4%) patients were followed up, for a mean of 7 years. Patients were evaluated according to a functional evaluation scale and outcome categories proposed by us. The scale takes account of tumor (recurrences and their eventual evolution); visual functions; endocrine functions (mainly hypothalamic), attainment of endocrine balance and drug regimen; headache; and psychosocial function. Recurrences were observed in 17.6% of patients treated with radical surgery and in 42.8% of those treated with limited surgery plus radiotherapy. A progressive amelioration of visual, endocrine and neuropsychosocial functions from the intervention to follow-up was observed in the majority of patients. Complete tumor excision was associated in 85% of cases with a low score on the functional scale, reflecting a high functional performance. Adequate substitution therapy maintained endocrine balance in 81% of patients. Since the intervention a progressive decrease in the number and dosages of medications has been observed. The majority of patients were again able to lead a normal social life. Small stature, obesity, headache, and emotional and sexual disturbances were frequent cause of long-term disability even despite adequate drug regimens. The functional evaluation scale we propose is a simple and effective tool that can be easily used during routine evaluation of patients with craniopharyngioma.

Assessment of Cure and Recurrence After Pituitary Surgery for Cushing's Disease

Summary Background. The treatment of choice in Cushings disease is transsphenoidal adenomectomy with a recurrence rate ranging 9–23%. We investigated whether abnormal hormonal responses may predict the relapse in “operated” patients followed-up for a long period. Method. Sixty-eight surgically treated patients with Cushings disease were followed-up for 12–252 months. Forty-eight patients underwent selective adenomectomy, 17 enlarged adenomectomy and 3 underwent total hypophysectomy. After surgery ACTH and cortisol levels were measured after stimulatory (desmopressin and CRH) and inhibitory tests (dexamethasone and loperamide). Findings. After operation 46 patients were cured (group A), 15 patients only normalized cortisol levels (group B), 7 patients were surgical failures. During the follow-up, a disease-free condition was maintained in 48 of 61 cases (79%), while a recurrence occurred in 13 patients (21%, 5 of group A and 8 of group B). In 5/13 patients who relapsed an absent inhibition after dexamethasone and an exaggerated response to CRH test preceded the recurrence. In 5 other patients the relapse was suspected by loperamide test. In the 3 remaining cases, positive responses to desmopressin preceded the recurrence. In 7/13 patients who relapsed the pituitary tumour was visualized by MRI/CT imaging. Interpretation. During the follow-up a careful assessment of ACTH dynamics is needed. Although no single test can reliably predict the late outcome, individual patients at risk for relapse may be identified by abnormal responses to desmopressin, CRH and loperamide tests; particularly, the persistent responsiveness to desmopressin may be a criterion of risk for recurrence in patients who only normalized cortisol levels after surgery.

Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma.

Purpose: We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth. Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR). Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined. Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.

Follow-Up Study of Brain Stem Tumors in Children

In a series of 180 patients affected by brain stem tumors, 70 cases of children up to 16 years are analyzed. Diagnosis was made with clinical examinations, neuroradiological tests and, in 20 cases, with surgical explorations. A description is made concerning the clinical status with regard to site, extension and features of the tumor. Then the authors analyze statistically the survival of such patients in connection with clinical symptomatology, the radiological picture, medical treatment, radiation and/or surgical therapy either in the few cases of subtotal removal of the tumors, or in the more numerous cases of palliative procedures such as intra- and extra-thecal CSF shunting.

Morphology and neurophysiology of focal axonal injury experimentally induced in the guinea pig optic nerve

SummaryA new model of focal axonal injury was reproduced by rapid and controlled elongation (uniaxial stretch) of the guinea pig optic nerve. Light microscopy study of optic nerve specimens after horseradish peroxidase injection into the vitreous of the animals eye showed that axonal lesions were identical to those seen in human and primate post-traumatic diffuse axonal injury (DAI). The lesions were characterized by the formation of terminal clubs in severed axons and focal axonal enlargements in those axons that were lesioned-in-continuity. Visual-evoked potentials upon flash stimulation were recorded before and after injury. Mean amplitude and mean latency of occipital peaks were significantly elongated in the acute post-traumatic phase. Electron microscopy examination showed that the main axonal changes observed in this model were cytoskeleton disorganization, accumulation of axoplasm membrane-bound bodies at the site of terminal balls and dilatations-in-continuity and detachment of the axolemma from the myelin sheath. Such axonal alterations were similar to those found in many other biological models of central and peripheral axonal injuries in which the lesion was produced by invasive methods. This model is unique since it reproduces the same mechanism of injury and the identical lesions that have been demonstrated in humans and primates with post-traumatic (DAI).

PATIENTS WITH MODERATE HEAD INJURY: A PROSPECTIVE MULTICENTER STUDY OF 315 PATIENTS

OBJECTIVETo analyze the risk factors of worst outcome associated with moderate head injury. METHODSData on patients with moderate head injury were collected prospectively in 11 Italian neurosurgical units over a period of 18 months. Patients older than 18 years with blunt head injury and at least one Glasgow Coma Scale (GCS) score between 9 and 13 were enrolled. The outcome was determined at 6 months using the Glasgow Outcome Scale. RESULTSWe analyzed 315 patients. Initial computed tomographic scans showed a diffuse injury type I or II in 63%, a mass lesion in 35%, and traumatic subarachnoid hemorrhage in 42% of the patients. The risk of progression toward a mass lesion was 23% when the admission computed tomographic scan showed diffuse injury type I or II. An emergency craniotomy was performed in 22% of the patients, delayed surgery was performed in 14%, and both were performed in 25%. A favorable outcome was obtained in 74% of the patients. When the GCS score was 9 or 10, the predictor of worst outcome was a motor GCS score of 4 or lower (odds ratio [OR], 8.08; 95% confidence interval [CI], 1.22–67.35; P = 0.008), but when the GCS score was 11 to 13, the factors associated with worst outcome were neuroworsening (OR, 3.43; 95% CI, 1.45–8.17; P = 0.002), seizures (OR, 7.94; 95% CI, 1.18–64.48; P = 0.02), and medical complications (OR, 4.24; 95% CI, 1.74–10.33; P = 0.0006). CONCLUSIONThere is a high percentage of surgery and worsening on computed tomographic scans in patients with moderate head injury. Neuroworsening, seizures, and medical complications as outcome predictors were more strongly associated with a GCS score of 11 to 13, whereas a low motor GCS score was more outcome-related in patients with GCS scores of 9 and 10.

Combined treatment of fourth ventricle ependymomas: report of 26 cases

BACKGROUND This study investigated the relevance of prognostic factors and the impact of histological features in posterior fossa ependymoma. METHODS The charts of 26 patients (aged 1-59 years, mean 20.6 years; 11 adults) with posterior fossa ependymoma operated on between January 1983 and December 1994 were reviewed and patients followed up (mean: 93 months). RESULTS Gross total resection was performed in 18 patients (69%), subtotal in seven patients (27%), biopsy in one patient (4%). One patient (3.8%) developed respiratory complications and died. All patients underwent posterior fossa radiotherapy (5000 cGy) after surgery. Four children first received chemotherapy and then radiotherapy only when at least 3 years old. Eleven patients (42%) received radiotherapy and subsequently chemotherapy. The 5-year survival rate was 90% for adults and 40% for children (</= 6 years). CONCLUSIONS This review suggests that a) younger patients (</= 6 years), despite multimodality treatment, have a poor prognosis; b) the microanatomical location of the tumor (lateral recess, roof, and floor) influences the extent of tumor removal (p < 0.05); c) longer survivals are associated with complete removal (p < 0.05); d) the histological feature most often related to a poor prognosis is a high mitotic index (p < 0.05), whereas vascular proliferation (p = 0.149), necrosis (p = 0.215), nuclear atypia (p = 0.384) and high cellularity (p = 0.786) do not affect survival; e) histological classification (WHO) does not reflect different survival rates between ependymomas and anaplastic ependymomas (p = 0.082).

Traumatic intracerebellar hemorrhage: Clinicoradiological analysis of 81 patients

OBJECTIVE We report 81 patients with a traumatic intracerebellar hemorrhagic contusion or hematoma managed between 1996 and 1998 at 13 Italian neurosurgical centers. METHODS Each center provided data about patients’ clinicoradiological findings, management, and outcomes, which were retrospectively reviewed. RESULTS A poor result occurred in 36 patients (44.4%). Forty-five patients (55.6%) had favorable results. For the purpose of data analysis, patients were divided into two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group 1 (39/81 cases; GCS score, ≥8), the outcome was favorable in 95% of cases. In Group 2 (42/81 cases; GCS score, <8), the outcome was poor in 81% of cases. Twenty-seven patients underwent posterior fossa surgery. Factors correlating with outcome were GCS score, status of the basal cisterns and the fourth ventricle, associated supratentorial traumatic lesions, mechanism of injury, and intracerebellar clot size. Multivariate analysis showed significant independent prognostic effect only for GCS score (P = 0.000) and the concomitant presence of supratentorial lesions (P = 0.0035). CONCLUSION This study describes clinicoradiological findings and prognostic factors regarding traumatic cerebellar injury. A general consensus emerged from this analysis that a conservative approach can be considered a viable, safe treatment option for noncomatose patients with intracerebellar clots measuring less than or equal to 3 cm, except when associated with other extradural or subdural posterior fossa focal lesions. Also, a general consensus was reached that surgery should be recommended for all patients with clots larger than 3 cm. The pathogenesis, biomechanics, and optimal management criteria of these rare lesions are still unclear, and larger observational studies are necessary.

IS20I, a specific αvβ3 integrin inhibitor, reduces glioma growth in vivo

OBJECTIVE The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS20I on human malignant gliomas. METHODS The in vitro effects of IS20I were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS20I was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS IS20I reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS20I strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS20I induced endothelial and tumor cell apoptosis. In vivo, when IS20I was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS20I inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo.

Neuroendocrine, immunohistochemical, and ultrastructural study of pineal region tumors

Abstract: Thirteen patients with tumors in the pineal region were submitted to pre‐ and post‐operative blood sampling (08:00, 14:00, 20:00, and 02:00 hr) for three or four consecutive days. A single cerebrospinal fluid (CSF) sample was collected at surgery, and melatonin levels determined. In all patients, serum and CSF beta subunit of human chorionic gonadotrophin (βHCG), carcino embryonic antigen (CEA), and alpha‐fetoprotein (AFP) levels were measured. Histology revealed four pineocytomas, one pineoblastoma, four germinomas, one immature teratoma, one pilocytic astrocytoma, one lymphoma, and one meningioma. Serum and CSF levels of serological biomarkers were normal, except for one of the germinoma cases. In most patients, alteration either in the circadian rhythm or in the melatonin concentration was observed before surgery. In benign neoplasms the circadian rhythm was conserved. In pineoblastoma, lymphoma, and three out of four germinomas, melatonin concentrations were undetectable. In one case of germinoma, melatonin levels were high, with the circadian rhythm being abolished. According to conventional histology, all germinomas were similar. Therefore, in a rare case of pineal germinoma with high melatonin levels, the tissue was subjected to an in depth investigation (immunohistochemical and ultrastructural) in order to determine the pathology and the possible differences from the other typical germinomas. Results were compared to those provided from other pineal neoplasms. Electron microscopy examination detected the presence of clusters of intermediate filaments and numerous electrondense granules only in the case of a germinoma producing melatonin.