Effect of cognitive rehabilitation in a case of thalamic astrocytoma.

We describe the effectiveness of rehabilitative training for a neuropsychological deficit following the removal and treatment of a fibrillary astrocytoma (Grade II) in a young man. The rehabilitative training was based on cognitive and motivational techniques and has been carried out for a period of 3 months (2 times per week). The results, even if limited to a single case, seem to support the idea that cognitive rehabilitation should facilitate the brain's reorganization of basic cognitive functions in the neuro-oncologic field.

Diagnostic and prognostic value of 18F-DOPA PET and 1H-MR spectroscopy in pediatric supratentorial infiltrative gliomas: a comparative study.

BACKGROUND: (1)H-MR spectroscopy (MRS) and (18)F-dihydroxyphenylalanine (DOPA) PET are noninvasive imaging techniques able to assess metabolic features of brain tumors. The aim of this study was to compare diagnostic and prognostic information gathered by (18)F-DOPA PET and (1)H-MRS in children with supratentorial infiltrative gliomas or nonneoplastic brain lesions suspected to be gliomas. METHODS: We retrospectively analyzed 27 pediatric patients with supratentorial infiltrative brain lesions on conventional MRI (21 gliomas and 6 nonneoplastic lesions) who underwent (18)F-DOPA PET and (1)H-MRS within 2 weeks of each other. (1)H-MRS data (choline/N-acetylaspartate, choline-to-creatine ratios, and presence of lactate) and (18)F-DOPA uptake parameters (lesion-to-normal tissue and lesion-to-striatum ratios) were compared and correlated with histology, WHO tumor grade, and patient outcome. RESULTS: (1)H-MRS and (18)F-DOPA PET data were positively correlated. Sensitivity, specificity, and accuracy in distinguishing gliomas from nonneoplastic lesions were 95%, 83%, and 93% for (1)H-MRS and 76%, 83%, and 78% for (18)F-DOPA PET, respectively. No statistically significant differences were found between the 2 techniques (P > .05). Significant differences regarding (18)F-DOPA uptake and (1)H-MRS ratios were found between low-grade and high-grade gliomas (P≤.001 and P≤.04, respectively). On multivariate analysis, (18)F-DOPA uptake independently correlated with progression-free survival (P≤.05) and overall survival (P = .04), whereas (1)H-MRS did not show significant association with outcome. CONCLUSIONS: (1)H-MRS and (18)F-DOPA PET provide useful complementary information for evaluating the metabolism of pediatric brain lesions. (1)H-MRS represents the method of first choice for differentiating brain gliomas from nonneoplastic lesions.(18)F-DOPA uptake better discriminates low-grade from high-grade gliomas and is an independent predictor of outcome.

Primary sellar neuroblastoma. A new case and review of literature.

The primary intracranial development of olfactory neuroblastomas, outside olfactory epithelium, is rare. We report a case of primary sellar neuroblastoma without any aggressive histopathological features, managed solely surgically without adjuvant therapy, with good outcomes at 3 years. Primary sellar neuroblastomas mostly occur in women in the 4th decade with a context of a non-secreting pituitary tumour. Diagnosis is made on histopathological examination (small cells, fibrillary intercellular background, strong immunoreactivity for neurons markers, negative immunoreactivity for anterior pituitary hormones). Management is based on surgery. Adjuvant treatment is not consensual, largely depends on patient's conditions and aggressive histopathological features.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: long-term results.

PURPOSE: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. METHODS AND MATERIALS: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. RESULTS: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. CONCLUSIONS: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

Cranial reconstruction using bioabsorbable calcified triglyceride bone cement.

BACKGROUND: We report our experience on 6 cases of cranial reconstruction using bioabsorbable calcified triglyceride KRYPTONITE Bone Cement (Doctors Research Group). METHODS: Six patients underwent cranial reconstruction during the surgical removal of a supratentorial tumor between September 2008 and November 2009 at our department. In 5 patients, we performed the cranial reconstruction using KRYPTONITE Bone Cement and cranial fixations; in the remaining patient, we avoided cranial fixation systems or other bone sutures to obtain good aesthetic results in the frontal supraorbital region. Preoperatively and 7 days and 12 months after surgery, patients were assessed using craniocerebral magnetic resonance imaging and computed tomography (CT). RESULTS: We observed that this bone cement was an injectable liquid for up to 8 minutes after mixing, it became adhesive at 8 to 15 minutes, and it was then shaped for use. Brain and dural reconstructions were not protected when this bone cement was being poured into the craniotomy site because of the minimal exothermal reaction. After 8 minutes, additional expansion is limited to 10%; therefore, we took heightened awareness of the amount of cement needed to fill the bone defect. In all patients, postoperative craniocerebral CT scanning, at 7 days, showed perfect alignment of the craniotomical bone and optimal filling of bone defects. No complications occurred, and aesthetic result was good. Twelve months after surgery, craniocerebral CT scanning showed bioabsorbability and osteoconductivity of this cement. CONCLUSIONS: KRYPTONITE Bone Cement is a nonthermal conducting, radiopaque, nonmagnetic, lightweight, simple to prepare, and easily applicable and molded material. Moreover, it has adhesive, bioabsorbable, and osteoconductive properties. To our knowledge, we present the first case of cranial reconstruction using this cement without cranial fixation systems.

Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model.

Multimodal combinations of target agents with radiation and chemotherapy may enhance cancer treatment efficacy; however, despite these treatments, gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of indomethacin-loaded nanocapsules in an experimental glioma model. The rats treated with indomethacin-loaded nanocapsules demonstrated a significant reduction in tumor size and half of these animals presented just cells with characteristics of a residual tumor, as shown by immunostaining for nestin. Pathological analyses showed that the treated gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. An important finding of the present study is that indomethacin carried by polymeric nanocapsules achieved higher intracerebral drug concentrations than those of indomethacin in solution. Furthermore, indomethacin achieved a greater concentration in the hemisphere where the glioma was implanted, compared with the contralateral healthy hemisphere. Indomethacin-loaded nanocapsule treatment did not cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric nanocapsules are able to increase the intratumoral bioavailability of indomethacin and reduce the growth of implanted gliomas. Data suggest that indomethacin-loaded nanocapsules could offer new and potentially highly effective strategies for the treatment of malignant gliomas.

Is it appropriate to redefine the indication for stereotactic brain biopsy in the MRI Era? Correlation with final histological diagnosis in supratentorial gliomas.

BACKGROUND: The aim of this study was to evaluate the advisability of modifying the indications for stereotactic brain biopsy (SBB) in high- and low-grade supratentorial glial tumors in correlation with the diagnostic accuracy of magnetic resonance imaging (MRI). MATERIALS AND METHODS: We analyzed 174 cases of supratentorial glial lesions diagnosed by MRI before biopsy. On the basis of the MRI findings the patients were divided into two groups: high-grade (n=107) and low-grade (n=67) gliomas. All patients underwent CT-guided biopsy. Only one preoperative diagnosis was allowed. RESULTS: A final histological diagnosis was achieved in 95% of the 174 cases. In the group of high-grade gliomas (HGG) there was diagnostic coincidence in 87% of cases, reaching 100% in lesions of the corpus callosum. In 11 cases (10%) the histological analysis changed the presumptive diagnosis and the consequent management. In the group of low-grade gliomas (LGG) there was diagnostic coincidence in 63% (42 cases), whereas there was discordance in 30%: 10 cases were upgraded to anaplastic astrocytoma, and in 10 cases no tumors were observed at all. CONCLUSIONS: In the future, the histological diagnosis of glial tumors will include molecular genetic definition, thus making it crucial for management using the new therapeutic options. Today, the indications for biopsy in lesions mimicking high-grade gliomas are mainly linked to the site of the tumor, coexisting differential diagnoses or more than one treatment option. In lesions of the corpus callosum, histological analysis seems not to be required in order to proceed to complementary therapies. On the contrary, in lesions where MRI findings indicate low-grade gliomas, grading is crucial also in order to avoid treatment inappropriate in non-neoplastic lesions.

Prognostic value of detecting recurrent glioblastoma multiforme in surgical specimens from patients after radiotherapy: should pathology evaluation alter treatment decisions?

The prognostic significance of the histologic type and grade of gliomas at initial surgery is well established, but the value of histologic findings in resections after radiotherapy is unclear. Despite this uncertainty, pathologic interpretation of specimens after radiotherapy influences immediate treatment decisions. It is important to determine if, and to what extent, treatment decisions should be based on this information. We aimed to determine the prognostic value of pathologic evaluation in postradiation specimens from 54 patients with similar clinical features who underwent a second surgery for the treatment of radiologic worsening after external beam radiotherapy. We categorized the specimens from the second surgery as either recurrent tumor (category 1) or radionecrosis (category 2). Patients in category 1 had actively proliferating neoplasms with classical features of glioblastoma, whereas patients in category 2 had no evidence of tumor in their surgical specimens. Cases in which a clear-cut definition could not be made were labeled indeterminate (category 3). Despite the morphological evidence of tumor, there were no significant differences between categories 1 and 2 in any of the survival parameters tested. The only difference between groups was higher frequency of iodine 125 (125I) placement at second surgery in category 1 patients (P <.028). Patients in category 1 with or without 125I treatment had similar survival characteristics. We conclude that histopathologic evaluation of postradiotherapy specimens was not helpful in predicting outcome or dictating further management. A comprehensive prospective study with advanced radiologic, pathologic, and molecular analyses may be more useful to determine prognostically valuable parameters.

Stereotactic biopsy of brain tumours in the paediatric population.

OBJECTIVE: Our objective was to establish the role of stereotactic neurosurgical techniques in the management of brain tumours in children. MATERIALS AND METHODS: A retrospective analysis was conducted of all stereotactic procedures performed in a single centre between 1996 and 2001. The success rates of achieving histologic diagnosis and a correlation between radiologic and histologic diagnosis were examined. RESULTS: There were 7 boys and 7 girls with a mean age of 9.1 years (range: 4-15). Under general anaesthetic 15 procedures were performed in 14 patients: 12 diagnostic and 3 therapeutic; 10 with CT and 5 with MRI guidance; 10 lesions were supratentorial and 4 were in the pons. A definitive histologic diagnosis was established in 10 of the 12 cases (diagnostic yield 83%). The pre-operative radiological diagnosis was accurate for tumour type in only 75% of the cases. In 3 patients cyst aspiration was attempted: post-operatively the cyst size was decreased in 2 and unchanged in 1. Seizures and acute confusion following biopsy of a thalamic tumour occurred in 1 patient. Post-operative scans were performed in 7 patients and in 2 we noted small, clinically insignificant, haemorrhages at the biopsy site. There was no mortality and morbidity was 6.6%. CONCLUSIONS: This small series confirms that stereotactic procedures in children are safe, well tolerated, with a high diagnostic yield, which could be improved with the use of intraoperative histopathological examination.

Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging proton MR spectroscopy, echoplanar perfusion and diffusion-weighted MRI.

Developments in MRI have made it possible to use diffusion-weighted MRI, perfusion MRI and proton MR spectroscopy (MRS) to study lesions in the brain. We evaluated whether these techniques provide useful, complementary information for grading gliomas, in comparison with conventional MRI. We studied 17 patients with histologically verified gliomas, adding multivoxel proton MRS, echoplanar diffusion and perfusion MRI the a routine MRI examination. The maximum relative cerebral blood volume (CBV), minimum apparent diffusion coefficient (ADC) and metabolic peak area ratios in proton MRS were calculated in solid parts of tumours on the same slice from each imaging data set. The mean minimum ADC of the 13 high-grade gliomas (0.92+/-0.27 x 10(-3) mm(2)/s) was lower than that of the four low-grade gliomas (1.28+/-0.15 x 10(-3) mm(2)/s) ( P<0.05). Means of maximum choline (Cho)/N-acetylaspartate (NAA), Cho/creatine (Cr), Cho/Cr in normal brain (Cr-n) and minimum NAA/Cr ratios were 5.90+/-2.62, 4.73+/-2.22, 2.66+/-0.68 and 0.40+/-0.06, respectively, in the high-grade gliomas, and 1.65+/-1.37, 1.84+/-1.20, 1.61+/-1.29 and 1.65+/-1.61, respectively, in the low-grade gliomas. Significant differences were found on spectroscopy between the high- and low-grade gliomas ( P<0.05). Mean maximum relative CBV in the high-grade gliomas (6.10+/-3.98) was higher than in the low-grade gliomas (1.74+/-0.57) ( P<0.05). Echoplanar diffusion, perfusion MRI and multivoxel proton MRS can offer diagnostic information, not available with conventional MRI, in the assessment of glioma grade.

Discrimination of brain abscess and cystic tumor by in vivo proton magnetic resonance spectroscopy.

Proton magnetic resonance (MR) spectroscopy was evaluated for the differentiation of brain abscesses and cystic brain tumors. Proton MR spectroscopy was performed in vivo in two patients with brain abscess and eight patients with various cystic brain tumors (anaplastic astrocytoma, glioblastoma, and metastatic brain tumor). MR imaging with contrast medium demonstrated ring-like enhanced mass lesions in all patients. The various resonance peaks in proton MR spectra were assigned to metabolites according to chemical shifts. Treatment of the cystic brain lesions was based on the information from proton MR spectroscopy. Aspirated pus from one patient with brain abscess was examined using ex vivo proton MR spectroscopy. The in vivo spectra of brain abscess contained resonance peaks attributed to acetate, lactate, alanine, amino acids, and lipids in both cases, and an additional peak of succinate in one case. In vivo spectra of the neoplasms contained resonance peaks corresponding to lactate, lipids, choline, creatine, and N-acetyl aspartate. Proton MR spectroscopy is useful for discriminating brain abscess from cystic tumors with similar neuroimaging appearance, which is very important for determining the treatment strategy.

Chiasmatic low-grade glioma presenting with sacral intradural spinal metastasis.

Leptomeningeal metastasis of low-grade gliomas in children has been documented in several series, both at the time of diagnosis and at relapse. The authors report a unique case of chiasmatic low-grade astrocytoma presenting with signs and symptoms related to the metastatic site rather than the primary site. In this respect, the possibility of appearance of symptoms and signs related to leptomeningeal dissemination preceding the signs and symptoms belonging to the primary site should be considered in this type of benign tumours.

[Laser-induced interstitial induced hyperthermia of cerebral tumors with nuclear magnetic resonance tomography control]. / Laserinduzierte interstitielle Thermotherapie von zerebralen Tumoren unter kernspintomographischer Kontrolle.

PURPOSE: The purpose of our study was to determine the value of MRI in monitoring laser-induced interstitial thermotherapy (LITT) of cerebral neoplasms. MATERIALS AND METHODS: Sixteen patients with brain tumors were treated with LITT. The laser irradiation was performed within the MR unit and monitored with a temperature-sensitive T1-weighted 2D-FLASH sequence. RESULTS: During irradiation a gradually increasing central zone of high signal intensity was surrounded by an increasing area of reduced signal intensity. After therapy, the diameter of an enhancing rim at the outer border of the peripheral zone indicated total lesion size. On T2-weighted images the signal intensities were reversed. Total lesion size decreased during follow-up. CONCLUSION: MRI is suitable for monitoring LITT. However, the role of LITT in the treatment of brain tumors has still to be defined.

Immunohistochemical study of giant cell in glioblastoma.

The clinical and immunohistochemical features of supratentorial (5 patients) and cerebellar (1 patient) glioblastomas, in which giant cells were conspicuous were examined. Three of the patients died within 26 months after the first treatment, and the follow-up period is presently 1 year or less in the remaining patients. The giant cells either showed large and bizarre nuclei or were multinucleated. Both giant and smaller cells excluding neuronal, endothelial and infiltrative cells were positive for GFAP, vimentin, and alpha-1 anti-chymotrypsin. The strong positivity for PCNA staining indicated that the capacity of the giant cells to synthesis DNA was preserved. DNA fragmentation, measured by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling method, was observed in only 1 patient, who had received radiotherapy just before biopsy, and none of the patients showed bcl-2 positivity. Mutant type of p53 tumor suppressor gene was observed in the giant cells of 3 patients. Giant cell in glioblastoma is of glial origin, synthesizes DNA, and its progression may be related to tumor suppressor gene.

A comparison of survival between radiosurgery and stereotactic implants for malignant astrocytomas.

The purpose of this paper is to compare the survival of three groups of patients with high grade supratentorial gliomas who were treated on three sequential protocols with surgical resection, external beam fractionated radiotherapy and a boost to the residual contrasting enhancing mass by either interstitial brachytherapy (IB, n = 33), by interstitial thermoradiotherapy (IT, n = 25) or by stereotactic radiosurgery (SRS, n = 19). The primary aim of this study was to evaluate the role of different boosting techniques in the initial management of primary brain tumors. External beam radiotherapy doses were escalated from one study to the next so that the median doses given to the IB, the IT, and the SRS groups were 41.4 Gy, 48.4 Gy, and 59.4 Gy, respectively. The median dose of interstitial irradiation or stereotactic radiosurgery, were 40 Gy, 32.2 Gy and 10 Gy, respectively, for the same groups. Follow-up was such that all living patients had been followed for a minimum of 30, 27, 4 months in the IB, IT, and SRS groups, respectively; hence, twelve-month survival was 52% (95% CI: 34%-69%), 80% (95% CI: 64%-96%), and 51% (95% CI: 24%-78%) in the same respective groups. Using a multivariate Cox proportional hazards model, treatment with IT conferred a survival advantage over IB (p = 0.029). Furthermore, survival of patients treated with SRS did not significantly differ from that of patients treated with an implant with or without hyperthermia.(ABSTRACT TRUNCATED AT 250 WORDS)