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Biomedical subjects

Giovanni Broggi

Publications and source records attributed to Giovanni Broggi.

33 records · Page 2Linked to original sources

CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells.

CXCL12 (stromal cell-derived factor-1/CXCL12) regulates leukocyte, endothelial and hematopoietic precursor migration, bone-marrow myelopoiesis and angiogenesis. CXCL12 and its receptor CXCR4 are over-expressed in malignant gliomas, which are highly vascularized tumors with a poor prognosis. We studied the expression of CXCL12 and CXCR4 in glioma cell lines, endothelial cells, tissue sections and endocavitary fluids from patients with gliomas. We then analyzed the proliferative and the apoptotic effect of CXCL12 in endothelial cells and glioma primary cultures. We observed the release of CXCL12 in supernatants of human brain microvascular endothelial cells and at variable levels, in post-surgical endocavitary fluids. CXCL12 was expressed in both glioma and endothelial cells as assessed by immunostaining of surgical brain sections. CXCR4 was found in cells lines and primary cultures from malignant gliomas as well as in endothelial cells and was increased by vascular endothelial growth factor and basic fibroblast growth factor (bFGF). CXCL12 inhibited bFGF-induced proliferation of endothelial cells and increased the survival of endothelial cells. The survival of primary cells obtained from glioma specimens was also enhanced in the presence of CXCL12. We point out the presence and the release of CXCL12 in tumor microenvironment and we observed a modulating effect of CXCL12 on proliferation and survival of both endothelial and tumoral cells. Our data support in vivo studies suggesting a role in angiogenesis played by CXCL12, which could represent a possible prognostic factor.

Brain Neoplasms↗

A simple method to assess accuracy of deep brain stimulation electrode placement: pre-operative stereotactic CT + postoperative MR image fusion.

OBJECTIVE: To describe a method for the measurement of the accuracy of deep brain stimulation (DBS) electrode placement with the use of image fusion technologies. PATIENTS AND METHODS: Ten consecutive patients suffering from movement disorders underwent DBS electrode placement. Postoperative MR images were fused with the pre-operative stereotactic CT. The placement error in the anteroposterior, lateral and vertical planes was calculated. RESULTS: The anteroposterior mean error +/- SD was 0.61 +/- 0.22 mm (range 0.2-0.9 mm). The lateral mean error +/- SD was 0.65 +/- 0.27 mm (range 0.2-2.2 mm). The vertical mean error +/- SD was 0.82 +/- 0.31 mm (range 0.3-1.6 mm). CONCLUSIONS: This technique provides a simple and precise method for the evaluation of the accuracy of DBS electrode placement.

Adult↗

Meningiomas invading the superior sagittal sinus: surgical experience in 108 cases.

OBJECTIVE: Radical resection of meningiomas invading the superior sagittal sinus (SSS) presents several hazards. Some surgeons consider SSS invasion a contraindication for complete resection, and others advocate total resection with venous reconstruction. There is a lack of published large series to provide definitive guidelines for the surgical treatment of these complex cases. We report our 15-year experience with surgery of parasagittal meningiomas invading the SSS. METHODS: Between 1986 and 2001, 108 patients (73 women, 35 men; age range, 22-83 yr; mean age, 56.2 yr) underwent surgery at the Neurological Institute "C. Besta" of Milan for tumors invading the SSS. Parasagittal meningiomas not invading the SSS were excluded from this series. RESULTS: Simpson Grade I to II removal was achieved in 100 patients. Thirty patients with meningiomas totally occluding the SSS had complete resection of the encased portion of the sinus. Histological examination revealed 86 benign (79.6%), 16 atypical (14.8%), and 4 malignant (3.7%) meningiomas along with 2 hemangiopericytomas. There were two perioperative deaths. Serious complications included brain swelling (nine patients; 8.3%) and postoperative hematoma (two patients; 1.85%). Follow-up ranged from 19 to 223 months (mean, 79.5 mo). One patient was lost to follow-up. Tumors recurred in 15 patients (13.9%). After multivariate analysis, histological type, tumor size, and Simpson grade were confirmed as significant independent prognostic factors for recurrence. CONCLUSION: On the basis of our results, we conclude that if the sinus is partially invaded, it can be opened to obtain as complete a resection as possible and to attempt to preserve the patency of the sinus. If the sinus is obstructed, the portion of the sinus involved can be resected completely. In both situations, extreme care is vital to preservation of cortical veins, which may offer important collateral drainage. With our approach, good results are achieved and it is not necessary to reconstruct the sinus.

Adult↗

Operative findings and outcomes of microvascular decompression for trigeminal neuralgia in 35 patients affected by multiple sclerosis.

OBJECTIVE: The concept of vascular compression of the trigeminal root as the main etiological factor in idiopathic trigeminal neuralgia has achieved widespread acceptance, and microvascular decompression (MVD) is a well-established surgical procedure for its treatment. Multiple sclerosis (MS) has long been considered to be an absolute contraindication to MVD because of the supposed exclusive causative role of a demyelinating lesion affecting the trigeminal root entry zone. Magnetic resonance imaging preoperative identification of suspicious vessels along the cisternal course of the trigeminal nerve in MS patients raises the question of a possible causative role of vascular compression in MS patients. METHODS: We describe magnetic resonance imaging findings, surgical findings, and outcomes in 35 MS patients who underwent MVD for medically intractable trigeminal neuralgia. Results were assessed by clinical follow-up and periodic phone surveys. The mean follow-up was 44 months (range, 6-108 mo). RESULTS: Magnetic resonance imaging revealed the presence of demyelinating lesions affecting the brainstem trigeminal pathways of the painful side in 26 (74%) of 35 patients. During surgery, severe neurovascular compression at the trigeminal root entry zone was found in 16 (46%) of 35 patients. The long-term outcome was excellent in 39%, good in 14%, fair in 8%, and poor in 39% of patients. No statistically significant prognostic factor predicting good outcome could be found. There was no mortality, with a 2.5% long-term morbidity rate (facial nerve palsy in one patient). CONCLUSION: Results of MVD in trigeminal neuralgia MS patients are much less satisfactory than in the idiopathic group, indicating that central mechanisms play a major role in pain genesis.

Adult↗

Intracavitary VEGF, bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma.

Intracavitary levels of VEGF, bFGF, IL-8 and IL- 12 were evaluated by ELISA in 45 patients, 7 with recurrent anaplastic astrocytoma (rAA), 12 with glioblastoma (GBM) and 26 with recurrent glioblastoma (rGBM). In 25 patients plasma levels of the molecules were also quantitated. Twenty-three healthy controls were also studied for plasma concentrations of the same molecules. Plasma levels of VEGF (mean 33.89 +/- 6.71 pg/ml) and bFGF (mean 11.1 +/- 3.24 pg/ml) were higher in patients than in controls (mean 16.78 +/- 3.7 pg/ml for VEGF, mean 0.21 +/- 0.09 pg/ml for bFGF) (p = 0.04 and p = 0.001, respectively) while plasma IL-12 levels were lower (mean 45.6 +/- 1.5 pg/ml in patients, mean 79.7 +/- 1.3 pg/ml in controls) (p = 0.009). Intracavitary VEGF levels were 5-53.307 fold higher (mean 90,900 +/- 24,789 pg/ml) than in the corresponding plasma. Also IL-8 concentrations were higher in intracavitary fluid (mean 6,349.76 +/- 1,460.93 pg/ml) than in plasma (mean 43.44 +/- 24.82 pg/ml). Maximum VEGF levels were found in tumor fluid of recurrent glioblastoma patients (mean 147,678 +/- 39.903 pg/ml), intermediate levels in glioblastoma patients (mean 20,322 +/- 11,892 pg/ml) and lower levels in rAA patients (mean 9,111 +/- 5,789 pg/ml). The data also suggest that higher intracavitary levels of VEGF and IL-8, and lower IL-12 levels, may be correlated with shorter adjunctive survival times, but more data will need to be collected to establish this correlation clearly.

Brain Neoplasms↗

Chronic motor cortex stimulation for movement disorders: a promising perspective.

Five patients affected by thalamic hand and international myoclonus have been evaluated and selected for chronic motor cortex stimulation. A quadripolar electrode strip was placed epidurally under local anesthesia through an MR-image-guided single precentral burr hole placed following the morphologic recognition of the central sulcus. Intra-operative stimulation was used to induce muscle contraction at the affected site to confirm the correct placement of the electrode. A one-week trial period preceded the implant of an internal pace-maker under general anesthesia. A remarkable decrease in pain was reported by four patients together with the reduction of dystonia and rigidity in thalamic hand and marked decrease of intentional myoclonus. No complications or undesired side effects of electrode implant and stimulation were observed.

Adult↗

Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: first reported series.

OBJECTIVE: To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. METHODS: Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. RESULTS: Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. CONCLUSION: These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.

Adult↗

Disconnective hemispherectomy for hemispheric dysplasia.

Twelve patients suffering from intractable epilepsy and presenting with radiological evidence of diffuse hemispheric involvement of a dysplastic process, were treated by disconnective hemispherectomy, either functional hemispherectomy or peri-insular hemispherotomy. The median age at surgery was 4.5 years old and the interval between seizure onset and surgery, 3 years. All patients underwent a presurgical evaluation that led to the suggestion of disconnective hemispherectomy. Over 70% of patients have remained in Engel's seizure outcome class I since surgery and another 18% have had a satisfactory seizure outcome. There was one unexplained death and one case of early hydrocephalus. Hemispherectomy offers the possibility to improve seizure control in the majority of patients undergoing surgery for extensive dysplastic pathology of the hemisphere. Disconnective techniques reduce the rate of complications in this specific pathology.

Adolescent↗

Association of chromosome 10 losses and negative prognosis in oligoastrocytomas.

Oligoastrocytomas are mixed gliomas harboring different genetic alterations and with heterogeneous clinical evolution. We have looked for correlations between genetic losses and clinical evolution in 34 oligoastrocytomas. Loss of heterozygosity (LOH) with different microsatellite markers was studied on chromosomes 1p, 10q, 17p, and 19q. LOH on 1p was found in 44% of the tumors, on 10q in 24%, on 17p in 18%, and on 19q in 38%. LOH on 1p and 19q was combined in 29% of the patients. LOH on 1p was associated with significantly longer overall survival (p = 0.0092) and LOH on 10q with shorter overall survival (p = 0.0206). The observation that LOH on 10q predicts a short survival in oligoastrocytomas is novel and provides further evidence that genetic analysis may help to predict the clinical evolution of different gliomas, giving a more rationale basis to therapeutic options.

Adult↗

Image-guided endoscopic transnasal removal of recurrent pituitary adenomas.

OBJECTIVE: To assess the role that neuronavigation plays in assisting endoscopic transsphenoidal reoperations for recurrent pituitary adenomas. METHODS: During a 45-month period, 19 endoscopic endonasal transsphenoidal reoperations were performed for recurrent pituitary adenomas. In 11 of 19 patients, the procedure was performed with the aid of an optically guided system. Clinical records were reviewed retrospectively, with attention to the following: comparison of baseline clinical data, the duration of surgery, and the postoperative course and complications of both image-guided and non-image-guided endoscopic reoperations. In addition, to test the reliability of the neuronavigation system, we made measurements of intraoperative accuracy in five additional transnasal endoscopic procedures in "virgin" noses and sphenoidal sinuses. RESULTS: In both groups studied, we found no difference with regard to either morbidity or mortality, which were null. The mean setup time was 13 minutes shorter in non-image-guided procedures (P = 0.021), and the operative time was 36 minutes shorter in image-guided procedures (P = 0.038). No other statistically significant differences were found between the two groups. In all cases, we found that the system performed without malfunction. Continuous information regarding instrument location and trajectory was provided to the surgeon. Measurements of the intraoperative accuracy in the axial, coronal, and sagittal planes indicated a mean intraoperatively verified system error of 1.6 +/- 0.6 mm. CONCLUSION: Neuronavigation can be applied during endonasal transsphenoidal endoscopic surgery and requires a minimal amount of time. It makes reoperation easier, faster, and probably safer.

Adenoma↗

Parkinson disease.

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Activities of Daily Living↗